Caveolin-1对小鼠肝癌细胞转化、凋亡及N-聚糖分支合成的调节作用
|
摘要
胞膜窖(caveolae)是50～100nm烧瓶状的细胞膜结构,和信号传导密切相关。窖蛋白-1(caveolin-1)是胞膜窖的主要结构成分,在细胞内吞、胆固醇运输、信号传导、肿瘤转化中发挥着重要的作用。Caveolin-1(Cav-1)在肿瘤中是发挥抑癌作用还是促癌作用一直存在争论。在大多数肿瘤细胞如乳腺癌、肺癌、卵巢癌中发挥抑癌基因样作用,而在少数肿瘤如前列腺癌中则发挥癌基因样作用。然而目前对Cav-1在肝癌细胞中所发挥作用的研究尚少,对于Cav-1介导肝癌细胞凋亡、侵袭和转移的分子机制亦不十分清楚。
我们前期研究结果表明,Cav-1在小鼠肝癌细胞Hca-F和Hca-P中呈高表达,且前者高于后者,在Hepa1-6细胞中表达缺失。其中Hca-F具有高侵袭、高淋巴道转移潜能,Hca-P具有低侵袭、低淋巴道转移潜能,Hepa1-6无转移潜能。因此推测,Cav-1的表达可能在小鼠肝癌细胞恶性表型转化中发挥重要作用。大量的实验已经表明,肿瘤细胞的恶性行为很大程度上是由细胞表面形成过量的β1,6GlcNAc分支结构,进而产生多天线的N-糖链结构,从而改变了糖蛋白分子的生物学性状,使肿瘤细胞的生物学行为发生改变。然而,Cav-1是否影响小鼠肝癌细胞N-糖蛋白的β1, 6GlcNAc分支结构,有关报道较少。
CD147,又称基质金属蛋白酶诱导物(EMMPRIN),是属于免疫球蛋白超家族的跨膜糖蛋白,由于N-糖基化程度的不同,表现为分子量不同的高糖型(HG-CD147)和低糖型(LG-CD147)。已有研究证实,CD147在许多恶性肿瘤细胞中有表达,并能诱导基质金属蛋白酶产生,从而影响肿瘤细胞的侵袭和转移。
我们前期研究结果显示,HG-CD147和LG-CD147在小鼠肝癌细胞Hca-F,Hca-P和Hepa1-6中均有表达,且Hca-F细胞的表达强度明显高于Hca-P和Hepa1-6细胞。此外,Cav-1的表达有利于LG-CD147向HG-CD147的转化。然而,CD147在不同淋巴道转移潜能的小鼠肝癌细胞株中的糖链结构如何,Cav-1表达是否对CD147糖蛋白糖链的分支结构产生了影响,Cav-1如何调节CD147的糖基化,有关报道甚少。
本文在利用分子克隆、基因转染及RNA干扰等技术上调和下调Cav-1表达的基础上,1)观察Cav-1表达变化对小鼠肝癌细胞转化、凋亡、侵袭和转移等生物学行为的影响;2)阐明Cav-1介导小鼠肝癌细胞凋亡、侵袭和转移的分子机制;3)分析CD147在小鼠肝癌细胞株中的糖型结构,并初步探讨Cav-1对N-糖蛋白分支结构的调节作用。本研究实验结果如下:
1. pEGFP-N2/Cav-1表达载体构建及在小鼠肝癌Hepa1-6细胞中的稳定表达
利用RT-PCR从小鼠肺组织总RNA中成功克隆出546bp的Cav-1cDNA的24-557bp片断,重组阳性克隆经酶切和测序鉴定证实目的基因已正确插入pEGFP-N2表达载体中,且与载体上的GFP基因处于同一开放阅读框,记为pEGFP-N2/Cav-1。
利用脂质体转染技术,G418筛选获得2个稳定表达外源Cav-1的Hepa1-6细胞株,记为Hepa1-6/Cav-1。RT-PCR和Western-blot方法证实,外源Cav-1基因整合到Hepa1-6细胞基因组中。免疫细胞化学和电镜结果显示,Cav-1在Hepa1-6细胞胞膜和胞浆中均有表达。
2. Cav-1表达上调或下调对小鼠肝癌细胞转化及凋亡的影响
软琼脂克隆形成实验和体内致瘤实验结果显示,与转染空载体组细胞(Hepa1-6/mock)和未转染组细胞Hepa1-6比较,Hepa1-6/Cav-1组细胞集落形成数和体内成瘤能力明显增加(P < 0.05)。
RT-PCR和Western-blot结果显示,与scrambled siRNA和unrelated siRNA(control-siRNA)相比,Cav-1特异性siRNA(Cav-1-siRNA)能够有效下调Cav-1在小鼠肝癌H22细胞中的表达,并可持续至转染后3周左右。致瘤实验和TUNEL实验结果显示,与对照组细胞相比,Cav-1-siRNA转染的H22细胞(H22/Cav-1-siRNA)在软琼脂中的克隆形成数明显减少,体内成瘤能力下降,凋亡数增多(P < 0.05)。
3. Cav-1在放线菌素D诱导小鼠肝癌细胞凋亡中的作用及分子机制
Hoechst 33342染色结果显示,放线菌素D可诱导小鼠肝癌细胞发生凋亡,呈时间和浓度依赖性。TUNEL结果显示,Cav-1过表达减少放线菌素D诱导的Hepa1-6细胞凋亡数目;Cav-1下调增加Hca-F细胞凋亡数目,并增强Hca-F细胞对放线菌素D的敏感性。
Western-blot结果显示,Cav-1过表达上调survivin蛋白水平,降低活性caspase-3(active caspase-3)表达;Cav-1表达沉默降低survivin蛋白水平,升高active caspase-3表达。
4. Cav-1对小鼠肝癌细胞N-聚糖β1,6GlcNAc分支的调节
PHA-L Lectin-blot结果显示,当Cav-1表达沉默时,H22细胞总蛋白与PHA-L的结合信号减弱,β1,6GlcNAc分支形成受抑制;当Cav-1过表达时,Hepa1-6细胞总蛋白与PHA-L的结合信号增强,β1,6GlcNAc分支形成增加。基质胶侵袭实验和体内淋巴结转移实验结果显示,β1,6GlcNAc分支减少可抑制H22细胞的侵袭和转移能力,β1,6GlcNAc分支增多可增强Hepa1-6细胞的侵袭能力。
糖苷酶酶切实验结果显示,在小鼠肝癌Hca-F和Hepa1-6细胞中CD147为N-糖蛋白,LG-CD147均为高甘露糖型,HG-CD147分别为杂合型和复合型。免疫共沉淀及Lectin-blot分析结果显示,Cav-1过表达可增加CD147的平分型GlcNAc分支形成,而对β1,6GlcNAc分支无影响。
Real-time PCR结果显示,Hepa1-6/Cav-1细胞中N-乙酰氨基葡萄糖基转移酶Ⅲ(GnTⅢ)的mRNA表达水平较Hepa1-6中升高,GnTⅣ有所降低,GnTⅤ升高不显著。
结论:
1. Cav-1可正性调节小鼠肝癌细胞转化、生存、侵袭和转移等恶性表型,发挥癌基因样作用。
2. Cav-1在放线菌素D诱导小鼠肝癌细胞凋亡中发挥重要作用,可通过调节survivin/caspase-3生存通路介导细胞凋亡。
3. Cav-1可通过调节小鼠肝癌细胞N-聚糖β1,6GlcNAc分支的形成介导肿瘤细胞的侵袭和转移。
Caveolin-1 is a major structural protein of caveolae and plays important roles in signal transduction, cellular transformation and tumor metastasis. Currently, the exact functions of Cav-1in tumor remain controversial. Cav-1may act as a tumor suppressor in most (but not all) cancer cells, and Cav-1also acts as a tumor promoter in certain tumor cell types. Thus, the Cav-1gene has been regarded as both a tumor suppressor gene and an oncogene. However, the exact role of Cav-1in hepatoma remains unknown. Therefore, an understanding of the molecular mechanisms involved in tumor cell transformation and progression could be helpful in developing more effective treatments for hepatoma.
In previous study, we have reported that Cav-1was highly expressed in mouse hepatoma cells with lymphatic metastasis potential, and could increase their invasive ability by up-regulating CD147 glycosylation level. This suggested that Cav-1expression might be correlated with the malign- nant phenotypes of hepatoma cells. However, the role of Cav-1in cell transformation and apoptosis has not been reported. Here,the relationship between Cav-1expression and malignant phenotypes was studied through overexpression of Cav-1in Cav-1-negative mouse hepatoma Hepa1-6 cells and gene-specific suppression of Cav-1expression in Cav-1-positive Hca-F cells.
In this study, exogenous expression of Cav-1in Hepa1-6 cells increased their transformation potential both in vitro and in vivo, and prevented ActD- induced apoptosis via the activation of survivin-mediated survival pathway. By contrast, down-regulation of Cav-1in Hca-F cells using small inter- fering RNA significantly attenuated cell transformation ability, and induced apoptosis and enhanced cell sensitivity to ActD. These results suggest that Cav-1could play an active role in mediating cell transformation and survival as well as cell invasion, and thus acts as a tumor promoter in hepatoma cells. Moreover, Cav-1might be a potential target for gene and drug treatment of hepatoma.
In addition, to further explore the exact roles of Cav-1and the possible utility of Cav-1downregulation for hepatoma therapy, we used RNAi technique to knockdown the expression of Cav-1in H22 hepatoma cells. In the present study, we have examined the phenotypic changes, including transformation capability and apoptotic potential, resulting from the reduction of Cav-1expression in transfected H22 cells both in vitro and in vivo. The results showed that Cav-1-siRNA could effectively inhibit the expression of Cav-1in H22 cells, and attenuate the transformation and survival capability of H22 cells in vitro and in vivo. Thus, Cav-1gene can be regarded as a very good target gene in genetic therapy for hepatoma and the use of Cav-1-siRNA deserves further investigations as a novel approach to cancer therapy.
CD147, also known as matrix metalloproteinase inducer (EMMPRIN), is a highly glycosylated immunoglobulin superfamily transmembrane pro- tein. As a result of heterogeneous N-glycosylation, CD147 exists in both highly glycosylated form, HG-CD147 (40–60 kDa) and lowly glycosylated form, LG-CD147 (32 kDa). CD147 was enriched on the surface of many malignant tumor cells, and can induce matrix metalloproteinase (MMP) production, thereby affect tumor cell invasion and metastasis.Many studies have shown that the malignant phenotypes of tumor cells are correlated with the exce- ssive formation of cell surfaceβ1, 6GlcNAc branching structure. However, the effect of Cav-1on N-glycoproteinβ1, 6GlcNAc branch structure of mouse hepatoma cells is rarely reported.
Our previous study showed that the CD147 expression level in Hca-F cells was significantly higher than that in Hca-P and Hepa1-6 cells. Cav-1expression resulted in the transformation from LG-CD147 to HG-CD147. However, there are few reports on the sugar chain structure of CD147 in different lymphatic metastasis potential of mouse hepatoma cell lines. The mechanism of the effect of Cav-1 on the CD147 glycosylation remains undetermined.
In this study, we found that Cav-1silencing could inhibitβ1, 6GlcNAc branching formation, and decrease the invasive and metastasis ability of mouse hepatoma H22 cells. Conversely, Cav-1overexpression could upregulateβ1, 6GlcNAc branching formation, and increase the migratory and invasive ability of mouse hepatoma cells.
In conclusion, Cav-1plays an active role in mediating cell transformation and survival, and is therefore regarded as an oncogene in hepatoma cells. Cav-1is involved in the hepatoma cell apoptosis through regulation of survivin-mediated survival pathway. Cav-1is involved in the hepatoma cell invasion and metastasis through regulation of N-glycanβ1, 6GlcNAc branching formation. These findings may implicate, at least partially, that Cav-1could represent an appropriate target for drug treatment of hepatoma.
我们前期研究结果表明,Cav-1在小鼠肝癌细胞Hca-F和Hca-P中呈高表达,且前者高于后者,在Hepa1-6细胞中表达缺失。其中Hca-F具有高侵袭、高淋巴道转移潜能,Hca-P具有低侵袭、低淋巴道转移潜能,Hepa1-6无转移潜能。因此推测,Cav-1的表达可能在小鼠肝癌细胞恶性表型转化中发挥重要作用。大量的实验已经表明,肿瘤细胞的恶性行为很大程度上是由细胞表面形成过量的β1,6GlcNAc分支结构,进而产生多天线的N-糖链结构,从而改变了糖蛋白分子的生物学性状,使肿瘤细胞的生物学行为发生改变。然而,Cav-1是否影响小鼠肝癌细胞N-糖蛋白的β1, 6GlcNAc分支结构,有关报道较少。
CD147,又称基质金属蛋白酶诱导物(EMMPRIN),是属于免疫球蛋白超家族的跨膜糖蛋白,由于N-糖基化程度的不同,表现为分子量不同的高糖型(HG-CD147)和低糖型(LG-CD147)。已有研究证实,CD147在许多恶性肿瘤细胞中有表达,并能诱导基质金属蛋白酶产生,从而影响肿瘤细胞的侵袭和转移。
我们前期研究结果显示,HG-CD147和LG-CD147在小鼠肝癌细胞Hca-F,Hca-P和Hepa1-6中均有表达,且Hca-F细胞的表达强度明显高于Hca-P和Hepa1-6细胞。此外,Cav-1的表达有利于LG-CD147向HG-CD147的转化。然而,CD147在不同淋巴道转移潜能的小鼠肝癌细胞株中的糖链结构如何,Cav-1表达是否对CD147糖蛋白糖链的分支结构产生了影响,Cav-1如何调节CD147的糖基化,有关报道甚少。
本文在利用分子克隆、基因转染及RNA干扰等技术上调和下调Cav-1表达的基础上,1)观察Cav-1表达变化对小鼠肝癌细胞转化、凋亡、侵袭和转移等生物学行为的影响;2)阐明Cav-1介导小鼠肝癌细胞凋亡、侵袭和转移的分子机制;3)分析CD147在小鼠肝癌细胞株中的糖型结构,并初步探讨Cav-1对N-糖蛋白分支结构的调节作用。本研究实验结果如下:
1. pEGFP-N2/Cav-1表达载体构建及在小鼠肝癌Hepa1-6细胞中的稳定表达
利用RT-PCR从小鼠肺组织总RNA中成功克隆出546bp的Cav-1cDNA的24-557bp片断,重组阳性克隆经酶切和测序鉴定证实目的基因已正确插入pEGFP-N2表达载体中,且与载体上的GFP基因处于同一开放阅读框,记为pEGFP-N2/Cav-1。
利用脂质体转染技术,G418筛选获得2个稳定表达外源Cav-1的Hepa1-6细胞株,记为Hepa1-6/Cav-1。RT-PCR和Western-blot方法证实,外源Cav-1基因整合到Hepa1-6细胞基因组中。免疫细胞化学和电镜结果显示,Cav-1在Hepa1-6细胞胞膜和胞浆中均有表达。
2. Cav-1表达上调或下调对小鼠肝癌细胞转化及凋亡的影响
软琼脂克隆形成实验和体内致瘤实验结果显示,与转染空载体组细胞(Hepa1-6/mock)和未转染组细胞Hepa1-6比较,Hepa1-6/Cav-1组细胞集落形成数和体内成瘤能力明显增加(P < 0.05)。
RT-PCR和Western-blot结果显示,与scrambled siRNA和unrelated siRNA(control-siRNA)相比,Cav-1特异性siRNA(Cav-1-siRNA)能够有效下调Cav-1在小鼠肝癌H22细胞中的表达,并可持续至转染后3周左右。致瘤实验和TUNEL实验结果显示,与对照组细胞相比,Cav-1-siRNA转染的H22细胞(H22/Cav-1-siRNA)在软琼脂中的克隆形成数明显减少,体内成瘤能力下降,凋亡数增多(P < 0.05)。
3. Cav-1在放线菌素D诱导小鼠肝癌细胞凋亡中的作用及分子机制
Hoechst 33342染色结果显示,放线菌素D可诱导小鼠肝癌细胞发生凋亡,呈时间和浓度依赖性。TUNEL结果显示,Cav-1过表达减少放线菌素D诱导的Hepa1-6细胞凋亡数目;Cav-1下调增加Hca-F细胞凋亡数目,并增强Hca-F细胞对放线菌素D的敏感性。
Western-blot结果显示,Cav-1过表达上调survivin蛋白水平,降低活性caspase-3(active caspase-3)表达;Cav-1表达沉默降低survivin蛋白水平,升高active caspase-3表达。
4. Cav-1对小鼠肝癌细胞N-聚糖β1,6GlcNAc分支的调节
PHA-L Lectin-blot结果显示,当Cav-1表达沉默时,H22细胞总蛋白与PHA-L的结合信号减弱,β1,6GlcNAc分支形成受抑制;当Cav-1过表达时,Hepa1-6细胞总蛋白与PHA-L的结合信号增强,β1,6GlcNAc分支形成增加。基质胶侵袭实验和体内淋巴结转移实验结果显示,β1,6GlcNAc分支减少可抑制H22细胞的侵袭和转移能力,β1,6GlcNAc分支增多可增强Hepa1-6细胞的侵袭能力。
糖苷酶酶切实验结果显示,在小鼠肝癌Hca-F和Hepa1-6细胞中CD147为N-糖蛋白,LG-CD147均为高甘露糖型,HG-CD147分别为杂合型和复合型。免疫共沉淀及Lectin-blot分析结果显示,Cav-1过表达可增加CD147的平分型GlcNAc分支形成,而对β1,6GlcNAc分支无影响。
Real-time PCR结果显示,Hepa1-6/Cav-1细胞中N-乙酰氨基葡萄糖基转移酶Ⅲ(GnTⅢ)的mRNA表达水平较Hepa1-6中升高,GnTⅣ有所降低,GnTⅤ升高不显著。
结论:
1. Cav-1可正性调节小鼠肝癌细胞转化、生存、侵袭和转移等恶性表型,发挥癌基因样作用。
2. Cav-1在放线菌素D诱导小鼠肝癌细胞凋亡中发挥重要作用,可通过调节survivin/caspase-3生存通路介导细胞凋亡。
3. Cav-1可通过调节小鼠肝癌细胞N-聚糖β1,6GlcNAc分支的形成介导肿瘤细胞的侵袭和转移。
Caveolin-1 is a major structural protein of caveolae and plays important roles in signal transduction, cellular transformation and tumor metastasis. Currently, the exact functions of Cav-1in tumor remain controversial. Cav-1may act as a tumor suppressor in most (but not all) cancer cells, and Cav-1also acts as a tumor promoter in certain tumor cell types. Thus, the Cav-1gene has been regarded as both a tumor suppressor gene and an oncogene. However, the exact role of Cav-1in hepatoma remains unknown. Therefore, an understanding of the molecular mechanisms involved in tumor cell transformation and progression could be helpful in developing more effective treatments for hepatoma.
In previous study, we have reported that Cav-1was highly expressed in mouse hepatoma cells with lymphatic metastasis potential, and could increase their invasive ability by up-regulating CD147 glycosylation level. This suggested that Cav-1expression might be correlated with the malign- nant phenotypes of hepatoma cells. However, the role of Cav-1in cell transformation and apoptosis has not been reported. Here,the relationship between Cav-1expression and malignant phenotypes was studied through overexpression of Cav-1in Cav-1-negative mouse hepatoma Hepa1-6 cells and gene-specific suppression of Cav-1expression in Cav-1-positive Hca-F cells.
In this study, exogenous expression of Cav-1in Hepa1-6 cells increased their transformation potential both in vitro and in vivo, and prevented ActD- induced apoptosis via the activation of survivin-mediated survival pathway. By contrast, down-regulation of Cav-1in Hca-F cells using small inter- fering RNA significantly attenuated cell transformation ability, and induced apoptosis and enhanced cell sensitivity to ActD. These results suggest that Cav-1could play an active role in mediating cell transformation and survival as well as cell invasion, and thus acts as a tumor promoter in hepatoma cells. Moreover, Cav-1might be a potential target for gene and drug treatment of hepatoma.
In addition, to further explore the exact roles of Cav-1and the possible utility of Cav-1downregulation for hepatoma therapy, we used RNAi technique to knockdown the expression of Cav-1in H22 hepatoma cells. In the present study, we have examined the phenotypic changes, including transformation capability and apoptotic potential, resulting from the reduction of Cav-1expression in transfected H22 cells both in vitro and in vivo. The results showed that Cav-1-siRNA could effectively inhibit the expression of Cav-1in H22 cells, and attenuate the transformation and survival capability of H22 cells in vitro and in vivo. Thus, Cav-1gene can be regarded as a very good target gene in genetic therapy for hepatoma and the use of Cav-1-siRNA deserves further investigations as a novel approach to cancer therapy.
CD147, also known as matrix metalloproteinase inducer (EMMPRIN), is a highly glycosylated immunoglobulin superfamily transmembrane pro- tein. As a result of heterogeneous N-glycosylation, CD147 exists in both highly glycosylated form, HG-CD147 (40–60 kDa) and lowly glycosylated form, LG-CD147 (32 kDa). CD147 was enriched on the surface of many malignant tumor cells, and can induce matrix metalloproteinase (MMP) production, thereby affect tumor cell invasion and metastasis.Many studies have shown that the malignant phenotypes of tumor cells are correlated with the exce- ssive formation of cell surfaceβ1, 6GlcNAc branching structure. However, the effect of Cav-1on N-glycoproteinβ1, 6GlcNAc branch structure of mouse hepatoma cells is rarely reported.
Our previous study showed that the CD147 expression level in Hca-F cells was significantly higher than that in Hca-P and Hepa1-6 cells. Cav-1expression resulted in the transformation from LG-CD147 to HG-CD147. However, there are few reports on the sugar chain structure of CD147 in different lymphatic metastasis potential of mouse hepatoma cell lines. The mechanism of the effect of Cav-1 on the CD147 glycosylation remains undetermined.
In this study, we found that Cav-1silencing could inhibitβ1, 6GlcNAc branching formation, and decrease the invasive and metastasis ability of mouse hepatoma H22 cells. Conversely, Cav-1overexpression could upregulateβ1, 6GlcNAc branching formation, and increase the migratory and invasive ability of mouse hepatoma cells.
In conclusion, Cav-1plays an active role in mediating cell transformation and survival, and is therefore regarded as an oncogene in hepatoma cells. Cav-1is involved in the hepatoma cell apoptosis through regulation of survivin-mediated survival pathway. Cav-1is involved in the hepatoma cell invasion and metastasis through regulation of N-glycanβ1, 6GlcNAc branching formation. These findings may implicate, at least partially, that Cav-1could represent an appropriate target for drug treatment of hepatoma.
引文
1 YAMADA,E. The fine structure of the renal glomerulus of the mouse, J.Bio- phys.Biochem.Cytol., 1: 551-566, 1955.
2 Song,K.S., Li,S., Okamoto,T., Quilliam,L.A., Sargiacomo,M. and Lisanti,M.P. Co-purification and direct interaction of Ras with caveolin, an integral me- mbrane protein of caveolae microdomains. Detergent-free purification of caveolae microdomains, J.Biol.Chem., 271: 9690-9697, 1996.
3 Fielding,C.J. and Fielding,P.E. Cholesterol and caveolae: structural and func- tional relationships, Biochim.Biophys.Acta, 1529: 210-222, 2000.
4 Stan,R.V. Structure of caveolae, Biochim.Biophys.Acta, 1746: 334-348, 2005.
5 Razani,B., Woodman,S.E. and Lisanti,M.P. Caveolae: from cell biology to ani- mal physiology, Pharmacol.Rev., 54: 431-467, 2002.
6 Galbiati,F., Razani,B. and Lisanti,M.P. Emerging themes in lipid rafts and cav- eolae, Cell, 106: 403-411, 2001.
7 Cohen,A.W., Razani,B., Schubert,W., Williams,T.M., Wang,X.B., Iyengar,P., Brasaemle,D.L., Scherer,P.E. and Lisanti,M.P. Role of caveolin-1 in the modula- tion of lipolysis and lipid droplet formation, Diabetes, 53: 1261-1270, 2004.
8 Engelman,J.A., Zhang,X.L. and Lisanti,M.P. Sequence and detailed organization of the human caveolin-1 and -2 genes located near the D7S522 locus (7q31.1). Methylation of a CpG island in the 5' promoter region of the caveolin-1 gene in human breast cancer cell lines, FEBS Lett., 448: 221-230, 1999.
9 Razani,B., Park,D.S., Miyanaga,Y., Ghatpande,A., Cohen,J., Wang,X.B., Sche- rer,P.E., Evans,T. and Lisanti,M.P. Molecular cloning and developmental expre- ssion of the caveolin gene family in the amphibian Xenopus laevis, Bioche- mistry, 41: 7914-7924, 2002.
10 Hooper,N.M. Detergent-insoluble glycosphingolipid/cholesterol-rich membrane domains, lipid rafts and caveolae (review), Mol.Membr.Biol., 16: 145-156, 1999.
11 Schlegel,A. and Lisanti,M.P. A molecular dissection of caveolin-1 membrane attachment and oligomerization. Two separate regions of the caveolin-1 C-ter- minal domain mediate membrane binding and oligomer/oligomer interactions in vivo, J.Biol.Chem., 275: 21605-21617, 2000.
12 Sundivakkam,P.C., Kwiatek,A.M., Sharma,T.T., Minshall,R.D., Malik,A.B. andTiruppathi,C. Caveolin-1 scaffold domain interacts with TRPC1 and IP3R3 to regulate Ca2+ store release-induced Ca2+ entry in endothelial cells, Am.J. Physiol Cell Physiol, 296: C403-C413, 2009.
13 Razani,B., Wang,X.B., Engelman,J.A., Battista,M., Lagaud,G., Zhang,X.L., Kneitz,B., Hou,H., Jr., Christ,G.J., Edelmann,W. and Lisanti,M.P. Caveolin-2- deficient mice show evidence of severe pulmonary dysfunction without disrup- tion of caveolae, Mol.Cell Biol., 22: 2329-2344, 2002.
14 Machleidt,T., Li,W.P., Liu,P. and Anderson,R.G. Multiple domains in caveolin-1 control its intracellular traffic, J.Cell Biol., 148: 17-28, 2000.
15 Pol,A., Martin,S., Fernandez,M.A., Ingelmo-Torres,M., Ferguson,C., Enrich,C. and Parton,R.G. Cholesterol and fatty acids regulate dynamic caveolin traffic- king through the Golgi complex and between the cell surface and lipid bodies, Mol.Biol.Cell, 16: 2091-2105, 2005.
16 Thomsen,P., Roepstorff,K., Stahlhut,M. and van,D.B. Caveolae are highly im- mobile plasma membrane microdomains, which are not involved in consti- tutive endocytic trafficking, Mol.Biol.Cell, 13: 238-250, 2002.
17 Smart,E.J., Ying,Y.S., Conrad,P.A. and Anderson,R.G. Caveolin moves from caveolae to the Golgi apparatus in response to cholesterol oxidation, J.Cell Biol., 127: 1185-1197, 1994.
18 Uittenbogaard,A., Ying,Y. and Smart,E.J. Characterization of a cytosolic heat- shock protein-caveolin chaperone complex. Involvement in cholesterol traffick- ing, J.Biol.Chem., 273: 6525-6532, 1998.
19 Li,W.P., Liu,P., Pilcher,B.K. and Anderson,R.G. Cell-specific targeting of cav- eolin-1 to caveolae, secretory vesicles, cytoplasm or mitochondria, J.Cell Sci., 114: 1397-1408, 2001.
20 Liu,P., Li,W.P., Machleidt,T. and Anderson,R.G. Identification of caveolin-1 in lipoprotein particles secreted by exocrine cells, Nat.Cell Biol., 1: 369-375, 1999.
21 Tahir,S.A., Yang,G., Ebara,S., Timme,T.L., Satoh,T., Li,L., Goltsov,A., Ittmann, M., Morrisett,J.D. and Thompson,T.C. Secreted caveolin-1 stimulates cell survi- val/clonal growth and contributes to metastasis in androgen-insensitive prostate cancer, Cancer Res., 61: 3882-3885, 2001.
22 Tahir,S.A., Yang,G., Goltsov,A.A., Watanabe,M., Tabata,K., Addai,J., Fattah el,M.A., Kadmon,D. and Thompson,T.C. Tumor cell-secreted caveolin-1 hasproangiogenic activities in prostate cancer, Cancer Res., 68: 731-739, 2008.
23 Fong,A., Garcia,E., Gwynn,L., Lisanti,M.P., Fazzari,M.J. and Li,M. Expression of caveolin-1 and caveolin-2 in urothelial carcinoma of the urinary bladder correlates with tumor grade and squamous differentiation, Am.J.Clin.Pathol., 120: 93-100, 2003.
24 Parton,R.G. and Simons,K. The multiple faces of caveolae, Nat.Rev.Mol.Cell Biol., 8: 185-194, 2007.
25 Park,S.S., Kim,J.E., Kim,Y.A., Kim,Y.C. and Kim,S.W. Caveolin-1 is down- regulated and inversely correlated with HER2 and EGFR expression status in invasive ductal carcinoma of the breast, Histopathology, 47: 625-630, 2005.
26 Belanger,M.M., Roussel,E. and Couet,J. Caveolin-1 is down-regulated in human lung carcinoma and acts as a candidate tumor suppressor gene, Chest, 125: 106S, 2004.
27 Chan,T.F., Su,T.H., Yeh,K.T., Chang,J.Y., Lin,T.H., Chen,J.C., Yuang,S.S. and Chang,J.G. Mutational, epigenetic and expressional analyses of caveolin-1 gene in cervical cancers, Int.J.Oncol., 23: 599-604, 2003.
28 Bender,F.C., Reymond,M.A., Bron,C. and Quest,A.F. Caveolin-1 levels are down-regulated in human colon tumors, and ectopic expression of caveolin-1 in colon carcinoma cell lines reduces cell tumorigenicity, Cancer Res., 60: 5870-5878, 2000.
29 Tirado,O.M., Mateo-Lozano,S., Villar,J., Dettin,L.E., Llort,A., Gallego,S., Ban,J., Kovar,H. and Notario,V. Caveolin-1 (CAV1) is a target of EWS/FLI-1 and a key determinant of the oncogenic phenotype and tumorigenicity of Ewing's sarcoma cells, Cancer Res., 66: 9937-9947, 2006.
30 Juhasz,M., Chen,J., Tulassay,Z., Malfertheiner,P. and Ebert,M.P. Expression of caveolin-1 in gastrointestinal and extraintestinal cancers, J.Cancer Res.Clin. Oncol., 129: 493-497, 2003.
31 Yang,G., Addai,J., Ittmann,M., Wheeler,T.M. and Thompson,T.C. Elevated caveolin-1 levels in African-American versus white-American prostate cancer, Clin.Cancer Res., 6: 3430-3433, 2000.
32 Joo,H.J., Oh,D.K., Kim,Y.S., Lee,K.B. and Kim,S.J. Increased expression of caveolin-1 and microvessel density correlates with metastasis and poor prog- nosis in clear cell renal cell carcinoma, BJU.Int., 93: 291-296, 2004.
33 Rajjayabun,P.H., Garg,S., Durkan,G.C., Charlton,R., Robinson,M.C. and Mellon,J.K. Caveolin-1 expression is associated with high-grade bladder cancer, Urology, 58: 811-814, 2001.
34 Liquori,G.E., Caroppo,R., Mastrodonato,M., Scillitani,G. and Ferri,D. Co-secre- tion of soluble caveolin-1 and pepsinogen in the oesophagus of the red-legged frog Rana aurora aurora, Acta Histochem., 106: 21-27, 2004.
35 Aldred,M.A., Ginn-Pease,M.E., Morrison,C.D., Popkie,A.P., Gimm,O., Hoang- Vu,C.,Krause,U.,Dralle,H.,Jhiang,S.M.,Plass,C.and Eng,C.Caveolin-1 and cave- olin-2,together with three bone morphogenetic protein-related genes, may encode novel tumor suppressors down-regulated in sporadic follicular thyroid carcinogenesis, Cancer Res., 63: 2864-2871, 2003.
36 Ito,Y., Yoshida,H., Tomoda,C., Uruno,T., Takamura,Y., Miya,A., Kobayashi,K., Matsuzuka,F., Nakamura,Y., Kakudo,K., Kuma,K. and Miyauchi,A. Caveolin-1 and 14-3-3 sigma expression in follicular variant of thyroid papillary carcinoma, Pathol.Res.Pract., 201: 545-549, 2005.
37 Ito,Y., Yoshida,H., Nakano,K., Kobayashi,K., Yokozawa,T., Hirai,K., Matsu- zuka,F., Matsuura,N., Kakudo,K., Kuma,K. and Miyauchi,A. Caveolin-1 overex- pression is an early event in the progression of papillary carcinoma of the thyroid, Br.J.Cancer, 86: 912-916, 2002.
38 Cai,C. and Chen,J. Overexpression of caveolin-1 induces alteration of multidrug resistance in Hs578T breast adenocarcinoma cells, Int.J.Cancer, 111: 522-529, 2004.
39 Shatz,M. and Liscovitch,M. Caveolin-1 and cancer multidrug resistance: coor- dinate regulation of pro-survival proteins?, Leuk.Res., 28: 907-908, 2004.
40 Williams,T.M., Hassan,G.S., Li,J., Cohen,A.W., Medina,F., Frank,P.G., Pestell, R.G., Di,V.D., Loda,M. and Lisanti,M.P. Caveolin-1 promotes tumor progression in an autochthonous mouse model of prostate cancer: genetic ablation of Cav-1delays advanced prostate tumor development in tramp mice, J.Biol.Chem., 280: 25134-25145, 2005.
41 Di,V.D., Sotgia,F., Williams,T.M., Hassan,G.S., Capozza,F., Frank,P.G., Pestell, R.G., Loda,M., Freeman,M.R. and Lisanti,M.P. Caveolin-1 is required for the upregulation of fatty acid synthase (FASN), a tumor promoter, during prostate cancer progression, Cancer Biol.Ther., 6: 1263-1268, 2007.
42 Karam,J.A., Lotan,Y., Roehrborn,C.G., Ashfaq,R., Karakiewicz,P.I. and Shariat, S.F. Caveolin-1 overexpression is associated with aggressive prostate cancerrecurrence, Prostate, 67: 614-622, 2007.
43 Thompson,T.C., Timme,T.L., Li,L. and Goltsov,A. Caveolin-1, a metastasis- related gene that promotes cell survival in prostate cancer, Apoptosis., 4: 233-237, 1999.
44 Yang,G., Addai,J., Wheeler,T.M., Frolov,A., Miles,B.J., Kadmon,D. and Thom- pson,T.C. Correlative evidence that prostate cancer cell-derived caveolin-1 mediates angiogenesis, Hum.Pathol., 38: 1688-1695, 2007.
45 Li,L., Yang,G., Ebara,S., Satoh,T., Nasu,Y., Timme,T.L., Ren,C., Wang,J., Tahir, S.A. and Thompson,T.C. Caveolin-1 mediates testosterone-stimulated survival/ clonal growth and promotes metastatic activities in prostate cancer cells, Cancer Res., 61: 4386-4392, 2001.
46 Joo,H.J., Oh,D.K., Kim,Y.S., Lee,K.B. and Kim,S.J. Increased expression of caveolin-1 and microvessel density correlates with metastasis and poor prog- nosis in clear cell renal cell carcinoma, BJU.Int., 93: 291-296, 2004.
47 Campbell,L., Gumbleton,M. and Griffiths,D.F. Caveolin-1 overexpression pre- dicts poor disease-free survival of patients with clinically confined renal cell carcinoma, Br.J.Cancer, 89: 1909-1913, 2003.
48 Sunaga,N., Miyajima,K., Suzuki,M., Sato,M., White,M.A., Ramirez,R.D., Shay, J.W., Gazdar,A.F. and Minna,J.D. Different roles for caveolin-1 in the develop- ment of non-small cell lung cancer versus small cell lung cancer, Cancer Res., 64: 4277-4285, 2004.
49 Ho,C.C., Huang,P.H., Huang,H.Y., Chen,Y.H., Yang,P.C. and Hsu,S.M. Up-regu- lated caveolin-1 accentuates the metastasis capability of lung adenocarcinoma by inducing filopodia formation, Am.J.Pathol., 161: 1647-1656, 2002.
50 Savage,K., Lambros,M.B., Robertson,D., Jones,R.L., Jones,C., Mackay,A., James, M., Hornick,J.L., Pereira,E.M., Milanezi,F., Fletcher,C.D., Schmitt,F.C., Ashworth,A. and Reis-Filho,J.S. Caveolin 1 is overexpressed and amplified in a subset of basal-like and metaplastic breast carcinomas: a morphologic, ultra- structural, immunohistochemical, and in situ hybridization analysis, Clin. Cancer Res., 13: 90-101, 2007.
51 Cai,C. and Chen,J. Overexpression of caveolin-1 induces alteration of multidrug resistance in Hs578T breast adenocarcinoma cells, Int.J.Cancer, 111: 522-529, 2004.
52 Jia,L., Wang,S., Zhou,H., Cao,J., Hu,Y. and Zhang,J. Caveolin-1 up-regulatesCD147 glycosylation and the invasive capability of murine hepatocarcinoma cell lines, Int.J.Biochem.Cell Biol., 38: 1584-1593, 2006.
53 Zhou,H., Jia,L., Wang,S., Wang,H., Chu,H., Hu,Y., Cao,J. and Zhang,J. Diver- gent expression and roles for caveolin-1 in mouse hepatocarcinoma cell lines with varying invasive ability, Biochem.Biophys.Res.Commun., 345: 486-494, 2006.
54 Tahir,S.A., Yang,G., Ebara,S., Timme,T.L., Satoh,T., Li,L., Goltsov,A., Ittmann, M., Morrisett,J.D. and Thompson,T.C. Secreted caveolin-1 stimulates cell survi- val/clonal growth and contributes to metastasis in androgen-insensitive prostate cancer, Cancer Res., 61: 3882-3885, 2001.
55 Koleske,A.J., Baltimore,D. and Lisanti,M.P. Reduction of caveolin and caveolae in oncogenically transformed cells, Proc.Natl.Acad.Sci.U.S.A, 92: 1381-1385, 1995.
56 Fiucci,G., Ravid,D., Reich,R. and Liscovitch,M. Caveolin-1 inhibits ancho- rage-independent growth, anoikis and invasiveness in MCF-7 human breast cancer cells, Oncogene, 21: 2365-2375, 2002.
57 Chan,T.F., Su,T.H., Yeh,K.T., Chang,J.Y., Lin,T.H., Chen,J.C., Yuang,S.S. and Chang,J.G. Mutational, epigenetic and expressional analyses of caveolin-1 gene in cervical cancers, Int.J.Oncol., 23: 599-604, 2003.
58 Wiechen,K., Diatchenko,L., Agoulnik,A., Scharff,K.M., Schober,H., Arlt,K., Zhumabayeva,B., Siebert,P.D., Dietel,M., Schafer,R. and Sers,C. Caveolin-1 is down-regulated in human ovarian carcinoma and acts as a candidate tumor suppressor gene, Am.J.Pathol., 159: 1635-1643, 2001.
59 Patlolla,J.M., Swamy,M.V., Raju,J. and Rao,C.V. Overexpression of caveolin-1 in experimental colon adenocarcinomas and human colon cancer cell lines, Oncol.Rep., 11: 957-963, 2004.
60 Bender,F.C., Reymond,M.A., Bron,C. and Quest,A.F. Caveolin-1 levels are down-regulated in human colon tumors, and ectopic expression of caveolin-1 in colon carcinoma cell lines reduces cell tumorigenicity, Cancer Res., 60: 5870-5878, 2000.
61 Sagara,Y., Mimori,K., Yoshinaga,K., Tanaka,F., Nishida,K., Ohno,S., Inoue,H. and Mori,M. Clinical significance of Caveolin-1, Caveolin-2 and HER2/neu mRNA expression in human breast cancer, Br.J.Cancer, 91: 959-965, 2004.
62 Zhang,H., Su,L., Muller,S., Tighiouart,M., Xu,Z., Zhang,X., Shin,H.J., Hunt,J.,Sun,S.Y., Shin,D.M. and Chen,Z.G. Restoration of caveolin-1 expression suppresses growth and metastasis of head and neck squamous cell carcinoma, Br.J.Cancer, 99: 1684-1694, 2008.
63 Tahir,S.A., Yang,G., Ebara,S., Timme,T.L., Satoh,T., Li,L., Goltsov,A., Ittma- nn,M., Morrisett,J.D. and Thompson,T.C. Secreted caveolin-1 stimulates cell survival/clonal growth and contributes to metastasis in androgen-insensitive prostate cancer, Cancer Res., 61: 3882-3885, 2001.
64 Yang,G., Truong,L.D., Wheeler,T.M. and Thompson,T.C. Caveolin-1 expression in clinically confined human prostate cancer: a novel prognostic marker, Cancer Res., 59: 5719-5723, 1999.
65 Joo,H.J., Oh,D.K., Kim,Y.S., Lee,K.B. and Kim,S.J. Increased expression of caveolin-1 and microvessel density correlates with metastasis and poor prognosis in clear cell renal cell carcinoma, BJU.Int., 93: 291-296, 2004.
66 Campbell,L., Gumbleton,M. and Griffiths,D.F. Caveolin-1 overexpression pre- dicts poor disease-free survival of patients with clinically confined renal cell carcinoma, Br.J.Cancer, 89: 1909-1913, 2003.
67 Wang,S., Jia,L., Zhou,H., Shi,W. and Zhang,J. Knockdown of Caveolin-1 by siRNA Inhibits the Transformation of Mouse Hepatoma H22 Cells In Vitro and In Vivo, Oligonucleotides., 2009.
68 Wang,S., Jia,L., Zhou,H., Wang,X. and Zhang,J. Caveolin-1 promotes the trans- formation and anti-apoptotic ability of mouse hepatoma cells, IUBMB.Life, 60: 693-699, 2008.
69 Carver,L.A. and Schnitzer,J.E. Caveolae: mining little caves for new cancer targets, Nat.Rev.Cancer, 3: 571-581, 2003.
70 Liu,P. and Anderson,R.G. Compartmentalized production of ceramide at the cell surface, J.Biol.Chem., 270: 27179-27185, 1995.
71 Zundel,W. and Giaccia,A. Inhibition of the anti-apoptotic PI(3)K/Akt/Bad path- way by stress, Genes Dev., 12: 1941-1946, 1998.
72 Zundel,W., Swiersz,L.M. and Giaccia,A. Caveolin 1-mediated regulation of receptor tyrosine kinase-associated phosphatidylinositol 3-kinase activity by ceramide, Mol.Cell Biol., 20: 1507-1514, 2000.
73 Liu,J., Lee,P., Galbiati,F., Kitsis,R.N. and Lisanti,M.P. Caveolin-1 expression sensitizes fibroblastic and epithelial cells to apoptotic stimulation, Am.J. Physiol Cell Physiol, 280: C823-C835, 2001.
74 Ingueneau,C., Huynh-Do,U., Thiers,J.C., Negre-Salvayre,A., Salvayre,R. and Vindis,C. Caveolin-1 sensitizes vascular smooth muscle cells to mildly oxidized LDL-induced apoptosis, Biochem.Biophys.Res.Commun., 369: 889-893, 2008.
75 Podar,K., Tai,Y.T., Cole,C.E., Hideshima,T., Sattler,M., Hamblin,A., Mitsiades, N., Schlossman,R.L., Davies,F.E., Morgan,G.J., Munshi,N.C., Chauhan,D. and Anderson,K.C. Essential role of caveolae in interleukin-6- and insulin-like growth factor I-triggered Akt-1-mediated survival of multiple myeloma cells, J.Biol.Chem., 278: 5794-5801, 2003.
76 Timme,T.L., Goltsov,A., Tahir,S., Li,L., Wang,J., Ren,C., Johnston,R.N. and Thompson,T.C. Caveolin-1 is regulated by c-myc and suppresses c-myc-induced apoptosis, Oncogene, 19: 3256-3265, 2000.
77 Tso,C.L., McBride,W.H., Sun,J., Patel,B., Tsui,K.H., Paik,S.H., Gitlitz,B., Caliliw,R., van,O.A., Wu,L., deKernion,J. and Belldegrun,A. Androgen depriva- tion induces selective outgrowth of aggressive hormone-refractory prostate cancer clones expressing distinct cellular and molecular properties not present in parental androgen-dependent cancer cells, Cancer J., 6: 220-233, 2000.
78 Li,L., Ren,C.H., Tahir,S.A., Ren,C. and Thompson,T.C. Caveolin-1 maintains activated Akt in prostate cancer cells through scaffolding domain binding site interactions with and inhibition of serine/threonine protein phosphatases PP1 and PP2A, Mol.Cell Biol., 23: 9389-9404, 2003.
79 Li,L., Yang,G., Ebara,S., Satoh,T., Nasu,Y., Timme,T.L., Ren,C., Wang,J., Tahir, S.A. and Thompson,T.C. Caveolin-1 mediates testosterone-stimulated survival/ clonal growth and promotes metastatic activities in prostate cancer cells, Cancer Res., 61: 4386-4392, 2001.
80 Nasu,Y., Timme,T.L., Yang,G., Bangma,C.H., Li,L., Ren,C., Park,S.H., DeLeon, M., Wang,J. and Thompson,T.C. Suppression of caveolin expression induces androgen sensitivity in metastatic androgen-insensitive mouse prostate cancer cells, Nat.Med., 4: 1062-1064, 1998.
81 Wang,S., Jia,L., Zhou,H., Shi,W. and Zhang,J. Knockdown of Caveolin-1 by siRNA Inhibits the Transformation of Mouse Hepatoma H22 Cells In Vitro and In Vivo, Oligonucleotides., 2009.
82 Wang,S., Jia,L., Zhou,H., Wang,X. and Zhang,J. Caveolin-1 promotes the trans- formation and anti-apoptotic ability of mouse hepatoma cells, IUBMB.Life, 60: 693-699, 2008.
83 Zhao,X., Liu,Y., Ma,Q., Wang,X., Jin,H., Mehrpour,M. and Chen,Q. Caveolin-1 negatively regulates TRAIL-induced apoptosis in human hepatocarcinoma cells, Biochem.Biophys.Res.Commun., 378: 21-26, 2009.
84 Zhou,H., Jia,L., Wang,S., Wang,H., Chu,H., Hu,Y., Cao,J. and Zhang,J. Divergent expression and roles for caveolin-1 in mouse hepatocarcinoma cell lines with varying invasive ability, Biochem.Biophys.Res.Commun., 345: 486-494, 2006.
85 Fiucci,G., Ravid,D., Reich,R. and Liscovitch,M. Caveolin-1 inhibits anchorage- independent growth, anoikis and invasiveness in MCF-7 human breast cancer cells, Oncogene, 21: 2365-2375, 2002.
86 Labrecque,L., Royal,I., Surprenant,D.S., Patterson,C., Gingras,D. and Beliveau, R. Regulation of vascular endothelial growth factor receptor-2 activity by caveolin-1 and plasma membrane cholesterol, Mol.Biol.Cell, 14: 334-347, 2003.
1 Belanger,M.M., Roussel,E. and Couet,J. Caveolin-1 is down-regulated in human lung carcinoma and acts as a candidate tumor suppressor gene, Chest, 125: 106S, 2004.
2 Hino,M., Doihara,H., Kobayashi,K., Aoe,M. and Shimizu,N. Caveolin-1 as tumor suppressor gene in breast cancer, Surg.Today, 33: 486-490, 2003.
3 Wiechen,K., Diatchenko,L., Agoulnik,A., Scharff,K.M., Schober,H., Arlt,K., Zhumabayeva,B., Siebert,P.D., Dietel,M., Schafer,R. and Sers,C. Caveolin-1 is down-regulated in human ovarian carcinoma and acts as a candidate tumor suppressor gene, Am.J.Pathol., 159: 1635-1643, 2001.
4 Thompson,T.C., Timme,T.L., Li,L. and Goltsov,A. Caveolin-1, a metastasis- related gene that promotes cell survival in prostate cancer, Apoptosis., 4: 233-237, 1999.
5 Tamaskar,I., Choueiri,T.K., Sercia,L., Rini,B., Bukowski,R. and Zhou,M. Diff- erential expression of caveolin-1 in renal neoplasms, Cancer, 110: 776-782, 2007.
6 Zhou,H., Jia,L., Wang,S., Wang,H., Chu,H., Hu,Y., Cao,J. and Zhang,J. Diver- gent expression and roles for caveolin-1 in mouse hepatocarcinoma cell lines with varying invasive ability, Biochem.Biophys.Res.Commun., 345: 486-494, 2006.
7 Zhou,H., Jia,L., Wang,S., Wang,H., Chu,H., Hu,Y., Cao,J. and Zhang,J. Diver- gent expression and roles for caveolin-1 in mouse hepatocarcinoma cell lines with varying invasive ability, Biochem.Biophys.Res.Commun., 345: 486-494, 2006.
8 Jia,L., Wang,S., Zhou,H., Cao,J., Hu,Y. and Zhang,J. Caveolin-1 up-regulates CD147 glycosylation and the invasive capability of murine hepatocarcinoma cell lines, Int.J.Biochem.Cell Biol., 38: 1584-1593, 2006.
9 Cohen,A.W., Hnasko,R., Schubert,W. and Lisanti,M.P. Role of caveolae and caveolins in health and disease, Physiol Rev., 84: 1341-1379, 2004.
10 Engelman,J.A., Lee,R.J., Karnezis,A., Bearss,D.J., Webster,M., Siegel,P., Mu- ller,W.J., Windle,J.J., Pestell,R.G. and Lisanti,M.P. Reciprocal regulation of n- eu tyrosine kinase activity and caveolin-1 protein expression in vitro and in vi-vo. Implications for human breast cancer, J.Biol.Chem., 273: 20448-20455, 1998.
11 Park,S.S., Kim,J.E., Kim,Y.A., Kim,Y.C. and Kim,S.W. Caveolin-1 is down- re- gulated and inversely correlated with HER2 and EGFR expression status ininvasive ductal carcinoma of the breast, Histopathology, 47: 625-630, 2005.
12 Zhang,Q., Furukawa,K., Chen,H.H., Fujinawa,R., Kozutsumi,Y., Suzuki,A., Urano,T. and Furukawa,K. Down-regulation of caveolin-1 in mouse Lewis lung cancer P29 is a causal factor for the malignant properties in a high-metastatic subline, Oncol.Rep., 16: 289-294, 2006.
13 Belanger,M.M., Roussel,E. and Couet,J. Caveolin-1 is down-regulated in human lung carcinoma and acts as a candidate tumor suppressor gene, Chest, 125: 106S, 2004.
14 Racine,C., Belanger,M., Hirabayashi,H., Boucher,M., Chakir,J. and Couet,J. Reduction of caveolin 1 gene expression in lung carcinoma cell lines, Bioc- hem.Biophys.Res.Commun., 255: 580-586, 1999.
15 Schlott,T., Eiffert,H., Bohne,W., Landgrebe,J., Brunner,E., Spielbauer,B. and Knight,B. Chlamydia trachomatis modulates expression of tumor suppressor gene caveolin-1 and oncogene C-myc in the transformation zone of nonneo- plastic cervical tissue, Gynecol.Oncol., 98: 409-419, 2005.
16 Chan,T.F., Su,T.H., Yeh,K.T., Chang,J.Y., Lin,T.H., Chen,J.C., Yuang,S.S. and Chang,J.G. Mutational, epigenetic and expressional analyses of caveolin-1 gene in cervical cancers, Int.J.Oncol., 23: 599-604, 2003.
17 Bender,F.C., Reymond,M.A., Bron,C. and Quest,A.F. Caveolin-1 levels are do- wnregulated in human colon tumors, and ectopic expression of caveolin-1 in colon carcinoma cell lines reduces cell tumorigenicity, Cancer Res., 60: 5870- 5878, 2000.
18 Tirado,O.M., Mateo-Lozano,S., Villar,J., Dettin,L.E., Llort,A., Gallego,S., Ban, J., Kovar,H. and Notario,V. Caveolin-1 (CAV1) is a target of EWS/FLI-1 and a key determinant of the oncogenic phenotype and tumorigenicity of Ewing's sarcoma cells, Cancer Res., 66: 9937-9947, 2006.
19 Karam,J.A., Lotan,Y., Roehrborn,C.G., Ashfaq,R., Karakiewicz,P.I. and Shariat, S.F. Caveolin-1 overexpression is associated with aggressive prostate cancer recurrence, Prostate, 67: 614-622, 2007.
20 Joo,H.J., Oh,D.K., Kim,Y.S., Lee,K.B. and Kim,S.J. Increased expression of caveolin-1 and microvessel density correlates with metastasis and poor prog- nosis in clear cell renal cell carcinoma, BJU.Int., 93: 291-296, 2004.
21 Cormack,B.P., Valdivia,R.H. and Falkow,S. FACS-optimized mutants of the green fluorescent protein (GFP), Gene, 173: 33-38, 1996.
1 Fiucci,G., Ravid,D., Reich,R. and Liscovitch,M. Caveolin-1 inhibits anchorage- independent growth, anoikis and invasiveness in MCF-7 human breast cancer cells, Oncogene, 21: 2365-2375, 2002.
2 Lee,S.W., Reimer,C.L., Oh,P., Campbell,D.B. and Schnitzer,J.E. Tumor cell gro- wth inhibition by caveolin re-expression in human breast cancer cells, Onco- gene, 16: 1391-1397, 1998.
3 Cox,A.D. and Der,C.J. Biological assays for cellular transformation, Methods Enzymol., 238: 277-294, 1994.
4 Koleske,A.J., Baltimore,D. and Lisanti,M.P. Reduction of caveolin and caveolae in oncogenically transformed cells, Proc.Natl.Acad.Sci.U.S.A, 92: 1381-1385, 1995.
5 Sloan,E.K., Stanley,K.L. and Anderson,R.L. Caveolin-1 inhibits breast cancer growth and metastasis, Oncogene, 23: 7893-7897, 2004.
6 Hino,M., Doihara,H., Kobayashi,K., Aoe,M. and Shimizu,N. Caveolin-1 as tum- or suppressor gene in breast cancer, Surg.Today, 33: 486-490, 2003.
7 Fiucci,G., Ravid,D., Reich,R. and Liscovitch,M. Caveolin-1 inhibits anchorage- independent growth, anoikis and invasiveness in MCF-7 human breast cancer cells, Oncogene, 21: 2365-2375, 2002.
8 Belanger,M.M., Roussel,E. and Couet,J. Caveolin-1 is down-regulated in human lung carcinoma and acts as a candidate tumor suppressor gene, Chest, 125: 106S, 2004.
9 Racine,C., Belanger,M., Hirabayashi,H., Boucher,M., Chakir,J. and Couet,J. Reduction of caveolin 1 gene expression in lung carcinoma cell lines, Biochem. Biophys.Res.Commun., 255: 580-586, 1999.
10 Chan,T.F., Su,T.H., Yeh,K.T., Chang,J.Y., Lin,T.H., Chen,J.C., Yuang,S.S. and Chang,J.G. Mutational, epigenetic and expressional analyses of caveolin-1 gene in cervical cancers, Int.J.Oncol., 23: 599-604, 2003.
11 Wiechen,K., Diatchenko,L., Agoulnik,A., Scharff,K.M., Schober,H., Arlt,K., Zhumabayeva,B., Siebert,P.D., Dietel,M., Schafer,R. and Sers,C. Caveolin-1 is down-regulated in human ovarian carcinoma and acts as a candidate tumor sup- pressor gene, Am.J.Pathol., 159: 1635-1643, 2001.
12 Patlolla,J.M., Swamy,M.V., Raju,J. and Rao,C.V. Overexpression of caveolin-1in experimental colon adenocarcinomas and human colon cancer cell lines, Oncol.Rep., 11: 957-963, 2004.
13 Zhang,H., Su,L., Muller,S., Tighiouart,M., Xu,Z., Zhang,X., Shin,H.J., Hunt,J., Sun,S.Y., Shin,D.M. and Chen,Z.G. Restoration of caveolin-1 expression sup- presses growth and metastasis of head and neck squamous cell carcinoma, Br.J.Cancer, 99: 1684-1694, 2008.
14 Bender,F.C., Reymond,M.A., Bron,C. and Quest,A.F. Caveolin-1 levels are down-regulated in human colon tumors, and ectopic expression of caveolin-1 in colon carcinoma cell lines reduces cell tumorigenicity, Cancer Res., 60: 5870- 5878, 2000.
15 Sotgia,F., Del,G.F., Casimiro,M.C., Bonuccelli,G., Mercier,I., Whitaker-Menezes,D., Daumer,K.M., Zhou,J., Wang,C., Katiyar,S., Xu,H., Bosco,E., Quong,A.A., Aronow,B., Witkiewicz,A.K., Minetti,C., Frank,P.G., Jimenez,S.A., Knudsen, E.S., Pestell,R.G. and Lisanti,M.P. Caveolin-1-/- null mammary stromal fibrob- lasts share characteristics with human breast cancer-associated fibroblasts, Am.J.Pathol., 174: 746-761, 2009.
16 Sagara,Y., Mimori,K., Yoshinaga,K., Tanaka,F., Nishida,K., Ohno,S., Inoue,H. and Mori,M. Clinical significance of Caveolin-1, Caveolin-2 and HER2/neu mRNA expression in human breast cancer, Br.J.Cancer, 91: 959-965, 2004.
17 Zhou,H., Jia,L., Wang,S., Wang,H., Chu,H., Hu,Y., Cao,J. and Zhang,J. Diverge- nt expression and roles for caveolin-1 in mouse hepatocarcinoma cell lines with varying invasive ability, Biochem.Biophys.Res.Commun., 345: 486-494, 2006.
18 Kim,D.H. and Rossi,J.J. Strategies for silencing human disease using RNA interference, Nat.Rev.Genet., 8: 173-184, 2007.
19 Rana,T.M. Illuminating the silence: understanding the structure and function of small RNAs, Nat.Rev.Mol.Cell Biol., 8: 23-36, 2007.
20 Rossi,J.J. Realizing the promise of RNAi, Mol.Ther., 16: 810-811, 2008.
1 Williams,T.M. and Lisanti,M.P. Caveolin-1 in oncogenic transformation, cancer, and metastasis, Am.J.Physiol Cell Physiol, 288: C494-C506, 2005.
2 Liu,J., Lee,P., Galbiati,F., Kitsis,R.N. and Lisanti,M.P. Caveolin-1 expression sensitizes fibroblastic and epithelial cells to apoptotic stimulation, Am.J. Physiol Cell Physiol, 280: C823-C835, 2001.
3 Liu,J., Lee,P., Galbiati,F., Kitsis,R.N. and Lisanti,M.P. Caveolin-1 expression sensitizes fibroblastic and epithelial cells to apoptotic stimulation, Am.J. Physiol Cell Physiol, 280: C823-C835, 2001.
4 Ingueneau,C., Huynh-Do,U., Thiers,J.C., Negre-Salvayre,A., Salvayre,R. and Vindis,C. Caveolin-1 sensitizes vascular smooth muscle cells to mildly oxidized LDL-induced apoptosis, Biochem.Biophys.Res.Commun., 369: 889-893, 2008.
5 Timme,T.L., Goltsov,A., Tahir,S., Li,L., Wang,J., Ren,C., Johnston,R.N. and Thompson,T.C. Caveolin-1 is regulated by c-myc and suppresses c-myc-induced apoptosis, Oncogene, 19: 3256-3265, 2000.
6 Tso,C.L., McBride,W.H., Sun,J., Patel,B., Tsui,K.H., Paik,S.H., Gitlitz,B., Caliliw,R., van,O.A., Wu,L., deKernion,J. and Belldegrun,A. Androgen depr- ivation induces selective outgrowth of aggressive hormone-refractory prostate cancer clones expressing distinct cellular and molecular properties not present in parental androgen-dependent cancer cells, Cancer J., 6: 220-233, 2000.
7 Li,L., Ren,C.H., Tahir,S.A., Ren,C. and Thompson,T.C. Caveolin-1 maintains activated Akt in prostate cancer cells through scaffolding domain binding site interactions with and inhibition of serine/threonine protein phosphatases PP1 and PP2A, Mol.Cell Biol., 23: 9389-9404, 2003.
8 Li,L., Yang,G., Ebara,S., Satoh,T., Nasu,Y., Timme,T.L., Ren,C., Wang,J., Tahir, S.A. and Thompson,T.C. Caveolin-1 mediates testosterone-stimulated survival/ clonal growth and promotes metastatic activities in prostate cancer cells, Cancer Res., 61: 4386-4392, 2001.
9 Nasu,Y., Timme,T.L., Yang,G., Bangma,C.H., Li,L., Ren,C., Park,S.H., DeLeon, M., Wang,J. and Thompson,T.C. Suppression of caveolin expression induces androgen sensitivity in metastatic androgen-insensitive mouse prostate cancer cells, Nat.Med., 4: 1062-1064, 1998.
10 Wang,M.J., Liu,S., Liu,Y. and Zheng,D. Actinomycin D enhances TRAIL-induced caspase-dependent and -independent apoptosis in SH-SY5Y neuro- blastoma cells, Neurosci.Res., 59: 40-46, 2007.
11 Glazyrin,A.L., Chinni,S., Alhasan,S., Adsay,V.N., Vaitkevicius,V.K. and Sarkar, F.H. Molecular mechanism(s) of actinomycin-D induced sensitization of pan- creatic cancer cells to CD95 mediated apoptosis, Int.J.Oncol., 20: 201-205, 2002.
12 Kleeff,J., Kornmann,M., Sawhney,H. and Korc,M. Actinomycin D induces apo- ptosis and inhibits growth of pancreatic cancer cells, Int.J.Cancer, 86: 399-407, 2000.
13 Zundel,W., Swiersz,L.M. and Giaccia,A. Caveolin 1-mediated regulation of re- ceptor tyrosine kinase-associated phosphatidylinositol 3-kinase activity by ceramide, Mol.Cell Biol., 20: 1507-1514, 2000.
14 Altieri,D.C. Survivin, versatile modulation of cell division and apoptosis in cancer, Oncogene, 22: 8581-8589, 2003.
15 Fornaro,M., Plescia,J., Chheang,S., Tallini,G., Zhu,Y.M., King,M., Altieri,D.C. and Languino,L.R. Fibronectin protects prostate cancer cells from tumor ne- crosis factor-alpha-induced apoptosis via the AKT/survivin pathway, J.Biol. Chem., 278: 50402-50411, 2003.
1 Hakomori,S. Tumor malignancy defined by aberrant glycosylation and sphingo(glyco)lipid metabolism, Cancer Res., 56: 5309-5318, 1996.
2 Wang,L., Liang,Y., Li,Z., Cai,X., Zhang,W., Wu,G., Jin,J., Fang,Z., Yang,Y. and Zha,X. Increase in beta1-6 GlcNAc branching caused by N-acety-lglucosaminyltransferase V directs integrin beta1 stability in human hepatocellular carcinoma cell line SMMC-7721, J.Cell Biochem., 100: 230-241, 2007.
3 Dennis,J.W., Laferte,S., Waghorne,C., Breitman,M.L. and Kerbel,R.S. Beta 1-6 branching of Asn-linked oligosaccharides is directly associated with metastasis, Science, 236: 582-585, 1987.
4 Wang,S., Jia,L., Zhou,H., Wang,X. and Zhang,J. Caveolin-1 promotes the transformation and anti-apoptotic ability of mouse hepatoma cells, IUBMB.Life, 60: 693-699, 2008.
5 Nabeshima,K., Iwasaki,H., Koga,K., Hojo,H., Suzumiya,J. and Kikuchi,M. Emmprin (basigin/CD147): matrix metalloproteinase modulator and multifunctional cell recognition molecule that plays a critical role in cancer progression, Pathol.Int., 56: 359-367, 2006.
6 Yan,L., Zucker,S. and Toole,B.P. Roles of the multifunctional glycoprotein, emmprin (basigin; CD147), in tumour progression, Thromb.Haemost., 93: 199-204, 2005.
7 Muramatsu,T. and Miyauchi,T. Basigin (CD147): a multifunctional transmem- brane protein involved in reproduction, neural function, inflammation and tumor invasion, Histol.Histopathol., 18: 981-987, 2003.
8 Jia,L., Wang,S., Zhou,H., Cao,J., Hu,Y. and Zhang,J. Caveolin-1 up-regulates CD147 glycosylation and the invasive capability of murine hepatocarcinoma cell lines, Int.J.Biochem.Cell Biol., 38: 1584-1593, 2006.
9 Wang,L., Liang,Y., Li,Z., Cai,X., Zhang,W., Wu,G., Jin,J., Fang,Z., Yang,Y. and Zha,X. Increase in beta1-6 GlcNAc branching caused by N-acetylglucosaminyltransferase V directs integrin beta1 stability in human hepatocellular carcinoma cell line SMMC-7721, J.Cell Biochem., 100: 230-241, 2007.
10 Duffy,M.J., McGowan,P.M. and Gallagher,W.M. Cancer invasion and metastasis: changing views, J.Pathol., 214: 283-293, 2008.
11 Price,J.T. and Thompson,E.W. Mechanisms of tumour invasion and metastasis:emerging targets for therapy, Expert.Opin.Ther.Targets., 6: 217-233, 2002.
12 Williams,T.M. and Lisanti,M.P. Caveolin-1 in oncogenic transformation, cancer, and metastasis, Am.J.Physiol Cell Physiol, 288: C494-C506, 2005.
13 Freeze,H.H. Lectin affinity chromatography, Curr.Protoc.Protein Sci., Chapter 9: Unit, 2001.
14 Habermaas,S. and Spiess,E. Cell surface glycosylation and characterization of a differentially expressed glycoprotein in metastatic and non metastatic cell lines of the rat BSp73 tumor, Anticancer Res., 12: 1251-1258, 1992.
15 Kobata,A. Altered glycosylation of surface glycoproteins in tumor cells and its clinical application, Pigment Cell Res., 2: 304-308, 1989.
16 Yagel,S., Feinmesser,R., Waghorne,C., Lala,P.K., Breitman,M.L. and Dennis,J.W. Evidence that beta 1-6 branched Asn-linked oligosaccharides on metastatic tumor cells facilitate invasion of basement membranes, Int.J.Cancer, 44: 685-690, 1989.
17 Reddy,B.V. and Kalraiya,R.D. Sialilated beta1,6 branched N-oligosaccharides modulate adhesion, chemotaxis and motility of melanoma cells: Effect on invasion and spontaneous metastasis properties, Biochim.Biophys.Acta, 1760: 1393-1402, 2006.
18 Seberger,P.J. and Chaney,W.G. Control of metastasis by Asn-linked, beta1-6 branched oligosaccharides in mouse mammary cancer cells, Glycobiology, 9: 235-241, 1999.
19 Lu,Y., Pelling,J.C. and Chaney,W.G. Tumor cell surface beta 1-6 branched oligosaccharides and lung metastasis, Clin.Exp.Metastasis, 12: 47-54, 1994.
20 Liu,B., Lin,Y. and Yin,H. [Inhibition effect of Swainsonine on the growth and metastasis of gastric cancer in vivo], Zhonghua Zhong.Liu Za Zhi., 20: 168-170, 1998.
21 Newton,S.A., White,S.L., Humphries,M.J. and Olden,K. Swainsonine inhibition of spontaneous metastasis, J.Natl.Cancer Inst., 81: 1024-1028, 1989.
22 Dennis,J.W. Effects of swainsonine and polyinosinic:polycytidylic acid on murine tumor cell growth and metastasis, Cancer Res., 46: 5131-5136, 1986.
23 Xu,J., Xu,H.Y., Zhang,Q., Song,F., Jiang,J.L., Yang,X.M., Mi,L., Wen,N., Tian,R., Wang,L., Yao,H., Feng,Q., Zhang,Y., Xing,J.L., Zhu,P. and Chen,Z.N. HAb18G/CD147 functions in invasion and metastasis of hepatocellular carcinoma, Mol.Cancer Res., 5: 605-614, 2007.
24 Tang,W., Chang,S.B. and Hemler,M.E. Links between CD147 function, glycosylation, and caveolin-1, Mol.Biol.Cell, 15: 4043-4050, 2004.
25 Yang,X., Tang,J., Rogler,C.E. and Stanley,P. Reduced hepatocyte proliferation is the basis of retarded liver tumor progression and liver regeneration in mice lacking N-acetylglucosaminyltransferaseⅢ, Cancer Res., 63: 7753-7759, 2003.
26 Yang,X., Bhaumik,M., Bhattacharyya,R., Gong,S., Rogler,C.E. and Stanley,P. New evidence for an extra-hepatic role of N-acetylglucosaminyltransferaseⅢin the progression of diethylnitrosamine-induced liver tumors in mice, Cancer Res., 60: 3313-3319, 2000.
27 Guo,P., Chen,H.J., Wang,Q.Y. and Chen,H.L. Down regulation of N-acetylglu- cosaminyltransferase V facilitates all-transretinoic acid to induce apoptosis of human hepatocarcinoma cells, Mol.Cell Biochem., 284: 103-110, 2006.
28 Guo,H.B., Liu,F. and Chen,H.L. Increased susceptibility to apoptosis of human hepatocarcinoma cells transfected with antisense N-acetylglucosaminyltransfe- rase V cDNA, Biochem.Biophys.Res.Commun., 264: 509-517, 1999.
29 Sasai,K., Ikeda,Y., Ihara,H., Honke,K. and Taniguchi,N. Caveolin-1 regulates the functional localization of N-acetylglucosaminyltransferaseⅢwithin the golgi apparatus, J.Biol.Chem., 278: 25295-25301, 2003.
2 Song,K.S., Li,S., Okamoto,T., Quilliam,L.A., Sargiacomo,M. and Lisanti,M.P. Co-purification and direct interaction of Ras with caveolin, an integral me- mbrane protein of caveolae microdomains. Detergent-free purification of caveolae microdomains, J.Biol.Chem., 271: 9690-9697, 1996.
3 Fielding,C.J. and Fielding,P.E. Cholesterol and caveolae: structural and func- tional relationships, Biochim.Biophys.Acta, 1529: 210-222, 2000.
4 Stan,R.V. Structure of caveolae, Biochim.Biophys.Acta, 1746: 334-348, 2005.
5 Razani,B., Woodman,S.E. and Lisanti,M.P. Caveolae: from cell biology to ani- mal physiology, Pharmacol.Rev., 54: 431-467, 2002.
6 Galbiati,F., Razani,B. and Lisanti,M.P. Emerging themes in lipid rafts and cav- eolae, Cell, 106: 403-411, 2001.
7 Cohen,A.W., Razani,B., Schubert,W., Williams,T.M., Wang,X.B., Iyengar,P., Brasaemle,D.L., Scherer,P.E. and Lisanti,M.P. Role of caveolin-1 in the modula- tion of lipolysis and lipid droplet formation, Diabetes, 53: 1261-1270, 2004.
8 Engelman,J.A., Zhang,X.L. and Lisanti,M.P. Sequence and detailed organization of the human caveolin-1 and -2 genes located near the D7S522 locus (7q31.1). Methylation of a CpG island in the 5' promoter region of the caveolin-1 gene in human breast cancer cell lines, FEBS Lett., 448: 221-230, 1999.
9 Razani,B., Park,D.S., Miyanaga,Y., Ghatpande,A., Cohen,J., Wang,X.B., Sche- rer,P.E., Evans,T. and Lisanti,M.P. Molecular cloning and developmental expre- ssion of the caveolin gene family in the amphibian Xenopus laevis, Bioche- mistry, 41: 7914-7924, 2002.
10 Hooper,N.M. Detergent-insoluble glycosphingolipid/cholesterol-rich membrane domains, lipid rafts and caveolae (review), Mol.Membr.Biol., 16: 145-156, 1999.
11 Schlegel,A. and Lisanti,M.P. A molecular dissection of caveolin-1 membrane attachment and oligomerization. Two separate regions of the caveolin-1 C-ter- minal domain mediate membrane binding and oligomer/oligomer interactions in vivo, J.Biol.Chem., 275: 21605-21617, 2000.
12 Sundivakkam,P.C., Kwiatek,A.M., Sharma,T.T., Minshall,R.D., Malik,A.B. andTiruppathi,C. Caveolin-1 scaffold domain interacts with TRPC1 and IP3R3 to regulate Ca2+ store release-induced Ca2+ entry in endothelial cells, Am.J. Physiol Cell Physiol, 296: C403-C413, 2009.
13 Razani,B., Wang,X.B., Engelman,J.A., Battista,M., Lagaud,G., Zhang,X.L., Kneitz,B., Hou,H., Jr., Christ,G.J., Edelmann,W. and Lisanti,M.P. Caveolin-2- deficient mice show evidence of severe pulmonary dysfunction without disrup- tion of caveolae, Mol.Cell Biol., 22: 2329-2344, 2002.
14 Machleidt,T., Li,W.P., Liu,P. and Anderson,R.G. Multiple domains in caveolin-1 control its intracellular traffic, J.Cell Biol., 148: 17-28, 2000.
15 Pol,A., Martin,S., Fernandez,M.A., Ingelmo-Torres,M., Ferguson,C., Enrich,C. and Parton,R.G. Cholesterol and fatty acids regulate dynamic caveolin traffic- king through the Golgi complex and between the cell surface and lipid bodies, Mol.Biol.Cell, 16: 2091-2105, 2005.
16 Thomsen,P., Roepstorff,K., Stahlhut,M. and van,D.B. Caveolae are highly im- mobile plasma membrane microdomains, which are not involved in consti- tutive endocytic trafficking, Mol.Biol.Cell, 13: 238-250, 2002.
17 Smart,E.J., Ying,Y.S., Conrad,P.A. and Anderson,R.G. Caveolin moves from caveolae to the Golgi apparatus in response to cholesterol oxidation, J.Cell Biol., 127: 1185-1197, 1994.
18 Uittenbogaard,A., Ying,Y. and Smart,E.J. Characterization of a cytosolic heat- shock protein-caveolin chaperone complex. Involvement in cholesterol traffick- ing, J.Biol.Chem., 273: 6525-6532, 1998.
19 Li,W.P., Liu,P., Pilcher,B.K. and Anderson,R.G. Cell-specific targeting of cav- eolin-1 to caveolae, secretory vesicles, cytoplasm or mitochondria, J.Cell Sci., 114: 1397-1408, 2001.
20 Liu,P., Li,W.P., Machleidt,T. and Anderson,R.G. Identification of caveolin-1 in lipoprotein particles secreted by exocrine cells, Nat.Cell Biol., 1: 369-375, 1999.
21 Tahir,S.A., Yang,G., Ebara,S., Timme,T.L., Satoh,T., Li,L., Goltsov,A., Ittmann, M., Morrisett,J.D. and Thompson,T.C. Secreted caveolin-1 stimulates cell survi- val/clonal growth and contributes to metastasis in androgen-insensitive prostate cancer, Cancer Res., 61: 3882-3885, 2001.
22 Tahir,S.A., Yang,G., Goltsov,A.A., Watanabe,M., Tabata,K., Addai,J., Fattah el,M.A., Kadmon,D. and Thompson,T.C. Tumor cell-secreted caveolin-1 hasproangiogenic activities in prostate cancer, Cancer Res., 68: 731-739, 2008.
23 Fong,A., Garcia,E., Gwynn,L., Lisanti,M.P., Fazzari,M.J. and Li,M. Expression of caveolin-1 and caveolin-2 in urothelial carcinoma of the urinary bladder correlates with tumor grade and squamous differentiation, Am.J.Clin.Pathol., 120: 93-100, 2003.
24 Parton,R.G. and Simons,K. The multiple faces of caveolae, Nat.Rev.Mol.Cell Biol., 8: 185-194, 2007.
25 Park,S.S., Kim,J.E., Kim,Y.A., Kim,Y.C. and Kim,S.W. Caveolin-1 is down- regulated and inversely correlated with HER2 and EGFR expression status in invasive ductal carcinoma of the breast, Histopathology, 47: 625-630, 2005.
26 Belanger,M.M., Roussel,E. and Couet,J. Caveolin-1 is down-regulated in human lung carcinoma and acts as a candidate tumor suppressor gene, Chest, 125: 106S, 2004.
27 Chan,T.F., Su,T.H., Yeh,K.T., Chang,J.Y., Lin,T.H., Chen,J.C., Yuang,S.S. and Chang,J.G. Mutational, epigenetic and expressional analyses of caveolin-1 gene in cervical cancers, Int.J.Oncol., 23: 599-604, 2003.
28 Bender,F.C., Reymond,M.A., Bron,C. and Quest,A.F. Caveolin-1 levels are down-regulated in human colon tumors, and ectopic expression of caveolin-1 in colon carcinoma cell lines reduces cell tumorigenicity, Cancer Res., 60: 5870-5878, 2000.
29 Tirado,O.M., Mateo-Lozano,S., Villar,J., Dettin,L.E., Llort,A., Gallego,S., Ban,J., Kovar,H. and Notario,V. Caveolin-1 (CAV1) is a target of EWS/FLI-1 and a key determinant of the oncogenic phenotype and tumorigenicity of Ewing's sarcoma cells, Cancer Res., 66: 9937-9947, 2006.
30 Juhasz,M., Chen,J., Tulassay,Z., Malfertheiner,P. and Ebert,M.P. Expression of caveolin-1 in gastrointestinal and extraintestinal cancers, J.Cancer Res.Clin. Oncol., 129: 493-497, 2003.
31 Yang,G., Addai,J., Ittmann,M., Wheeler,T.M. and Thompson,T.C. Elevated caveolin-1 levels in African-American versus white-American prostate cancer, Clin.Cancer Res., 6: 3430-3433, 2000.
32 Joo,H.J., Oh,D.K., Kim,Y.S., Lee,K.B. and Kim,S.J. Increased expression of caveolin-1 and microvessel density correlates with metastasis and poor prog- nosis in clear cell renal cell carcinoma, BJU.Int., 93: 291-296, 2004.
33 Rajjayabun,P.H., Garg,S., Durkan,G.C., Charlton,R., Robinson,M.C. and Mellon,J.K. Caveolin-1 expression is associated with high-grade bladder cancer, Urology, 58: 811-814, 2001.
34 Liquori,G.E., Caroppo,R., Mastrodonato,M., Scillitani,G. and Ferri,D. Co-secre- tion of soluble caveolin-1 and pepsinogen in the oesophagus of the red-legged frog Rana aurora aurora, Acta Histochem., 106: 21-27, 2004.
35 Aldred,M.A., Ginn-Pease,M.E., Morrison,C.D., Popkie,A.P., Gimm,O., Hoang- Vu,C.,Krause,U.,Dralle,H.,Jhiang,S.M.,Plass,C.and Eng,C.Caveolin-1 and cave- olin-2,together with three bone morphogenetic protein-related genes, may encode novel tumor suppressors down-regulated in sporadic follicular thyroid carcinogenesis, Cancer Res., 63: 2864-2871, 2003.
36 Ito,Y., Yoshida,H., Tomoda,C., Uruno,T., Takamura,Y., Miya,A., Kobayashi,K., Matsuzuka,F., Nakamura,Y., Kakudo,K., Kuma,K. and Miyauchi,A. Caveolin-1 and 14-3-3 sigma expression in follicular variant of thyroid papillary carcinoma, Pathol.Res.Pract., 201: 545-549, 2005.
37 Ito,Y., Yoshida,H., Nakano,K., Kobayashi,K., Yokozawa,T., Hirai,K., Matsu- zuka,F., Matsuura,N., Kakudo,K., Kuma,K. and Miyauchi,A. Caveolin-1 overex- pression is an early event in the progression of papillary carcinoma of the thyroid, Br.J.Cancer, 86: 912-916, 2002.
38 Cai,C. and Chen,J. Overexpression of caveolin-1 induces alteration of multidrug resistance in Hs578T breast adenocarcinoma cells, Int.J.Cancer, 111: 522-529, 2004.
39 Shatz,M. and Liscovitch,M. Caveolin-1 and cancer multidrug resistance: coor- dinate regulation of pro-survival proteins?, Leuk.Res., 28: 907-908, 2004.
40 Williams,T.M., Hassan,G.S., Li,J., Cohen,A.W., Medina,F., Frank,P.G., Pestell, R.G., Di,V.D., Loda,M. and Lisanti,M.P. Caveolin-1 promotes tumor progression in an autochthonous mouse model of prostate cancer: genetic ablation of Cav-1delays advanced prostate tumor development in tramp mice, J.Biol.Chem., 280: 25134-25145, 2005.
41 Di,V.D., Sotgia,F., Williams,T.M., Hassan,G.S., Capozza,F., Frank,P.G., Pestell, R.G., Loda,M., Freeman,M.R. and Lisanti,M.P. Caveolin-1 is required for the upregulation of fatty acid synthase (FASN), a tumor promoter, during prostate cancer progression, Cancer Biol.Ther., 6: 1263-1268, 2007.
42 Karam,J.A., Lotan,Y., Roehrborn,C.G., Ashfaq,R., Karakiewicz,P.I. and Shariat, S.F. Caveolin-1 overexpression is associated with aggressive prostate cancerrecurrence, Prostate, 67: 614-622, 2007.
43 Thompson,T.C., Timme,T.L., Li,L. and Goltsov,A. Caveolin-1, a metastasis- related gene that promotes cell survival in prostate cancer, Apoptosis., 4: 233-237, 1999.
44 Yang,G., Addai,J., Wheeler,T.M., Frolov,A., Miles,B.J., Kadmon,D. and Thom- pson,T.C. Correlative evidence that prostate cancer cell-derived caveolin-1 mediates angiogenesis, Hum.Pathol., 38: 1688-1695, 2007.
45 Li,L., Yang,G., Ebara,S., Satoh,T., Nasu,Y., Timme,T.L., Ren,C., Wang,J., Tahir, S.A. and Thompson,T.C. Caveolin-1 mediates testosterone-stimulated survival/ clonal growth and promotes metastatic activities in prostate cancer cells, Cancer Res., 61: 4386-4392, 2001.
46 Joo,H.J., Oh,D.K., Kim,Y.S., Lee,K.B. and Kim,S.J. Increased expression of caveolin-1 and microvessel density correlates with metastasis and poor prog- nosis in clear cell renal cell carcinoma, BJU.Int., 93: 291-296, 2004.
47 Campbell,L., Gumbleton,M. and Griffiths,D.F. Caveolin-1 overexpression pre- dicts poor disease-free survival of patients with clinically confined renal cell carcinoma, Br.J.Cancer, 89: 1909-1913, 2003.
48 Sunaga,N., Miyajima,K., Suzuki,M., Sato,M., White,M.A., Ramirez,R.D., Shay, J.W., Gazdar,A.F. and Minna,J.D. Different roles for caveolin-1 in the develop- ment of non-small cell lung cancer versus small cell lung cancer, Cancer Res., 64: 4277-4285, 2004.
49 Ho,C.C., Huang,P.H., Huang,H.Y., Chen,Y.H., Yang,P.C. and Hsu,S.M. Up-regu- lated caveolin-1 accentuates the metastasis capability of lung adenocarcinoma by inducing filopodia formation, Am.J.Pathol., 161: 1647-1656, 2002.
50 Savage,K., Lambros,M.B., Robertson,D., Jones,R.L., Jones,C., Mackay,A., James, M., Hornick,J.L., Pereira,E.M., Milanezi,F., Fletcher,C.D., Schmitt,F.C., Ashworth,A. and Reis-Filho,J.S. Caveolin 1 is overexpressed and amplified in a subset of basal-like and metaplastic breast carcinomas: a morphologic, ultra- structural, immunohistochemical, and in situ hybridization analysis, Clin. Cancer Res., 13: 90-101, 2007.
51 Cai,C. and Chen,J. Overexpression of caveolin-1 induces alteration of multidrug resistance in Hs578T breast adenocarcinoma cells, Int.J.Cancer, 111: 522-529, 2004.
52 Jia,L., Wang,S., Zhou,H., Cao,J., Hu,Y. and Zhang,J. Caveolin-1 up-regulatesCD147 glycosylation and the invasive capability of murine hepatocarcinoma cell lines, Int.J.Biochem.Cell Biol., 38: 1584-1593, 2006.
53 Zhou,H., Jia,L., Wang,S., Wang,H., Chu,H., Hu,Y., Cao,J. and Zhang,J. Diver- gent expression and roles for caveolin-1 in mouse hepatocarcinoma cell lines with varying invasive ability, Biochem.Biophys.Res.Commun., 345: 486-494, 2006.
54 Tahir,S.A., Yang,G., Ebara,S., Timme,T.L., Satoh,T., Li,L., Goltsov,A., Ittmann, M., Morrisett,J.D. and Thompson,T.C. Secreted caveolin-1 stimulates cell survi- val/clonal growth and contributes to metastasis in androgen-insensitive prostate cancer, Cancer Res., 61: 3882-3885, 2001.
55 Koleske,A.J., Baltimore,D. and Lisanti,M.P. Reduction of caveolin and caveolae in oncogenically transformed cells, Proc.Natl.Acad.Sci.U.S.A, 92: 1381-1385, 1995.
56 Fiucci,G., Ravid,D., Reich,R. and Liscovitch,M. Caveolin-1 inhibits ancho- rage-independent growth, anoikis and invasiveness in MCF-7 human breast cancer cells, Oncogene, 21: 2365-2375, 2002.
57 Chan,T.F., Su,T.H., Yeh,K.T., Chang,J.Y., Lin,T.H., Chen,J.C., Yuang,S.S. and Chang,J.G. Mutational, epigenetic and expressional analyses of caveolin-1 gene in cervical cancers, Int.J.Oncol., 23: 599-604, 2003.
58 Wiechen,K., Diatchenko,L., Agoulnik,A., Scharff,K.M., Schober,H., Arlt,K., Zhumabayeva,B., Siebert,P.D., Dietel,M., Schafer,R. and Sers,C. Caveolin-1 is down-regulated in human ovarian carcinoma and acts as a candidate tumor suppressor gene, Am.J.Pathol., 159: 1635-1643, 2001.
59 Patlolla,J.M., Swamy,M.V., Raju,J. and Rao,C.V. Overexpression of caveolin-1 in experimental colon adenocarcinomas and human colon cancer cell lines, Oncol.Rep., 11: 957-963, 2004.
60 Bender,F.C., Reymond,M.A., Bron,C. and Quest,A.F. Caveolin-1 levels are down-regulated in human colon tumors, and ectopic expression of caveolin-1 in colon carcinoma cell lines reduces cell tumorigenicity, Cancer Res., 60: 5870-5878, 2000.
61 Sagara,Y., Mimori,K., Yoshinaga,K., Tanaka,F., Nishida,K., Ohno,S., Inoue,H. and Mori,M. Clinical significance of Caveolin-1, Caveolin-2 and HER2/neu mRNA expression in human breast cancer, Br.J.Cancer, 91: 959-965, 2004.
62 Zhang,H., Su,L., Muller,S., Tighiouart,M., Xu,Z., Zhang,X., Shin,H.J., Hunt,J.,Sun,S.Y., Shin,D.M. and Chen,Z.G. Restoration of caveolin-1 expression suppresses growth and metastasis of head and neck squamous cell carcinoma, Br.J.Cancer, 99: 1684-1694, 2008.
63 Tahir,S.A., Yang,G., Ebara,S., Timme,T.L., Satoh,T., Li,L., Goltsov,A., Ittma- nn,M., Morrisett,J.D. and Thompson,T.C. Secreted caveolin-1 stimulates cell survival/clonal growth and contributes to metastasis in androgen-insensitive prostate cancer, Cancer Res., 61: 3882-3885, 2001.
64 Yang,G., Truong,L.D., Wheeler,T.M. and Thompson,T.C. Caveolin-1 expression in clinically confined human prostate cancer: a novel prognostic marker, Cancer Res., 59: 5719-5723, 1999.
65 Joo,H.J., Oh,D.K., Kim,Y.S., Lee,K.B. and Kim,S.J. Increased expression of caveolin-1 and microvessel density correlates with metastasis and poor prognosis in clear cell renal cell carcinoma, BJU.Int., 93: 291-296, 2004.
66 Campbell,L., Gumbleton,M. and Griffiths,D.F. Caveolin-1 overexpression pre- dicts poor disease-free survival of patients with clinically confined renal cell carcinoma, Br.J.Cancer, 89: 1909-1913, 2003.
67 Wang,S., Jia,L., Zhou,H., Shi,W. and Zhang,J. Knockdown of Caveolin-1 by siRNA Inhibits the Transformation of Mouse Hepatoma H22 Cells In Vitro and In Vivo, Oligonucleotides., 2009.
68 Wang,S., Jia,L., Zhou,H., Wang,X. and Zhang,J. Caveolin-1 promotes the trans- formation and anti-apoptotic ability of mouse hepatoma cells, IUBMB.Life, 60: 693-699, 2008.
69 Carver,L.A. and Schnitzer,J.E. Caveolae: mining little caves for new cancer targets, Nat.Rev.Cancer, 3: 571-581, 2003.
70 Liu,P. and Anderson,R.G. Compartmentalized production of ceramide at the cell surface, J.Biol.Chem., 270: 27179-27185, 1995.
71 Zundel,W. and Giaccia,A. Inhibition of the anti-apoptotic PI(3)K/Akt/Bad path- way by stress, Genes Dev., 12: 1941-1946, 1998.
72 Zundel,W., Swiersz,L.M. and Giaccia,A. Caveolin 1-mediated regulation of receptor tyrosine kinase-associated phosphatidylinositol 3-kinase activity by ceramide, Mol.Cell Biol., 20: 1507-1514, 2000.
73 Liu,J., Lee,P., Galbiati,F., Kitsis,R.N. and Lisanti,M.P. Caveolin-1 expression sensitizes fibroblastic and epithelial cells to apoptotic stimulation, Am.J. Physiol Cell Physiol, 280: C823-C835, 2001.
74 Ingueneau,C., Huynh-Do,U., Thiers,J.C., Negre-Salvayre,A., Salvayre,R. and Vindis,C. Caveolin-1 sensitizes vascular smooth muscle cells to mildly oxidized LDL-induced apoptosis, Biochem.Biophys.Res.Commun., 369: 889-893, 2008.
75 Podar,K., Tai,Y.T., Cole,C.E., Hideshima,T., Sattler,M., Hamblin,A., Mitsiades, N., Schlossman,R.L., Davies,F.E., Morgan,G.J., Munshi,N.C., Chauhan,D. and Anderson,K.C. Essential role of caveolae in interleukin-6- and insulin-like growth factor I-triggered Akt-1-mediated survival of multiple myeloma cells, J.Biol.Chem., 278: 5794-5801, 2003.
76 Timme,T.L., Goltsov,A., Tahir,S., Li,L., Wang,J., Ren,C., Johnston,R.N. and Thompson,T.C. Caveolin-1 is regulated by c-myc and suppresses c-myc-induced apoptosis, Oncogene, 19: 3256-3265, 2000.
77 Tso,C.L., McBride,W.H., Sun,J., Patel,B., Tsui,K.H., Paik,S.H., Gitlitz,B., Caliliw,R., van,O.A., Wu,L., deKernion,J. and Belldegrun,A. Androgen depriva- tion induces selective outgrowth of aggressive hormone-refractory prostate cancer clones expressing distinct cellular and molecular properties not present in parental androgen-dependent cancer cells, Cancer J., 6: 220-233, 2000.
78 Li,L., Ren,C.H., Tahir,S.A., Ren,C. and Thompson,T.C. Caveolin-1 maintains activated Akt in prostate cancer cells through scaffolding domain binding site interactions with and inhibition of serine/threonine protein phosphatases PP1 and PP2A, Mol.Cell Biol., 23: 9389-9404, 2003.
79 Li,L., Yang,G., Ebara,S., Satoh,T., Nasu,Y., Timme,T.L., Ren,C., Wang,J., Tahir, S.A. and Thompson,T.C. Caveolin-1 mediates testosterone-stimulated survival/ clonal growth and promotes metastatic activities in prostate cancer cells, Cancer Res., 61: 4386-4392, 2001.
80 Nasu,Y., Timme,T.L., Yang,G., Bangma,C.H., Li,L., Ren,C., Park,S.H., DeLeon, M., Wang,J. and Thompson,T.C. Suppression of caveolin expression induces androgen sensitivity in metastatic androgen-insensitive mouse prostate cancer cells, Nat.Med., 4: 1062-1064, 1998.
81 Wang,S., Jia,L., Zhou,H., Shi,W. and Zhang,J. Knockdown of Caveolin-1 by siRNA Inhibits the Transformation of Mouse Hepatoma H22 Cells In Vitro and In Vivo, Oligonucleotides., 2009.
82 Wang,S., Jia,L., Zhou,H., Wang,X. and Zhang,J. Caveolin-1 promotes the trans- formation and anti-apoptotic ability of mouse hepatoma cells, IUBMB.Life, 60: 693-699, 2008.
83 Zhao,X., Liu,Y., Ma,Q., Wang,X., Jin,H., Mehrpour,M. and Chen,Q. Caveolin-1 negatively regulates TRAIL-induced apoptosis in human hepatocarcinoma cells, Biochem.Biophys.Res.Commun., 378: 21-26, 2009.
84 Zhou,H., Jia,L., Wang,S., Wang,H., Chu,H., Hu,Y., Cao,J. and Zhang,J. Divergent expression and roles for caveolin-1 in mouse hepatocarcinoma cell lines with varying invasive ability, Biochem.Biophys.Res.Commun., 345: 486-494, 2006.
85 Fiucci,G., Ravid,D., Reich,R. and Liscovitch,M. Caveolin-1 inhibits anchorage- independent growth, anoikis and invasiveness in MCF-7 human breast cancer cells, Oncogene, 21: 2365-2375, 2002.
86 Labrecque,L., Royal,I., Surprenant,D.S., Patterson,C., Gingras,D. and Beliveau, R. Regulation of vascular endothelial growth factor receptor-2 activity by caveolin-1 and plasma membrane cholesterol, Mol.Biol.Cell, 14: 334-347, 2003.
1 Belanger,M.M., Roussel,E. and Couet,J. Caveolin-1 is down-regulated in human lung carcinoma and acts as a candidate tumor suppressor gene, Chest, 125: 106S, 2004.
2 Hino,M., Doihara,H., Kobayashi,K., Aoe,M. and Shimizu,N. Caveolin-1 as tumor suppressor gene in breast cancer, Surg.Today, 33: 486-490, 2003.
3 Wiechen,K., Diatchenko,L., Agoulnik,A., Scharff,K.M., Schober,H., Arlt,K., Zhumabayeva,B., Siebert,P.D., Dietel,M., Schafer,R. and Sers,C. Caveolin-1 is down-regulated in human ovarian carcinoma and acts as a candidate tumor suppressor gene, Am.J.Pathol., 159: 1635-1643, 2001.
4 Thompson,T.C., Timme,T.L., Li,L. and Goltsov,A. Caveolin-1, a metastasis- related gene that promotes cell survival in prostate cancer, Apoptosis., 4: 233-237, 1999.
5 Tamaskar,I., Choueiri,T.K., Sercia,L., Rini,B., Bukowski,R. and Zhou,M. Diff- erential expression of caveolin-1 in renal neoplasms, Cancer, 110: 776-782, 2007.
6 Zhou,H., Jia,L., Wang,S., Wang,H., Chu,H., Hu,Y., Cao,J. and Zhang,J. Diver- gent expression and roles for caveolin-1 in mouse hepatocarcinoma cell lines with varying invasive ability, Biochem.Biophys.Res.Commun., 345: 486-494, 2006.
7 Zhou,H., Jia,L., Wang,S., Wang,H., Chu,H., Hu,Y., Cao,J. and Zhang,J. Diver- gent expression and roles for caveolin-1 in mouse hepatocarcinoma cell lines with varying invasive ability, Biochem.Biophys.Res.Commun., 345: 486-494, 2006.
8 Jia,L., Wang,S., Zhou,H., Cao,J., Hu,Y. and Zhang,J. Caveolin-1 up-regulates CD147 glycosylation and the invasive capability of murine hepatocarcinoma cell lines, Int.J.Biochem.Cell Biol., 38: 1584-1593, 2006.
9 Cohen,A.W., Hnasko,R., Schubert,W. and Lisanti,M.P. Role of caveolae and caveolins in health and disease, Physiol Rev., 84: 1341-1379, 2004.
10 Engelman,J.A., Lee,R.J., Karnezis,A., Bearss,D.J., Webster,M., Siegel,P., Mu- ller,W.J., Windle,J.J., Pestell,R.G. and Lisanti,M.P. Reciprocal regulation of n- eu tyrosine kinase activity and caveolin-1 protein expression in vitro and in vi-vo. Implications for human breast cancer, J.Biol.Chem., 273: 20448-20455, 1998.
11 Park,S.S., Kim,J.E., Kim,Y.A., Kim,Y.C. and Kim,S.W. Caveolin-1 is down- re- gulated and inversely correlated with HER2 and EGFR expression status ininvasive ductal carcinoma of the breast, Histopathology, 47: 625-630, 2005.
12 Zhang,Q., Furukawa,K., Chen,H.H., Fujinawa,R., Kozutsumi,Y., Suzuki,A., Urano,T. and Furukawa,K. Down-regulation of caveolin-1 in mouse Lewis lung cancer P29 is a causal factor for the malignant properties in a high-metastatic subline, Oncol.Rep., 16: 289-294, 2006.
13 Belanger,M.M., Roussel,E. and Couet,J. Caveolin-1 is down-regulated in human lung carcinoma and acts as a candidate tumor suppressor gene, Chest, 125: 106S, 2004.
14 Racine,C., Belanger,M., Hirabayashi,H., Boucher,M., Chakir,J. and Couet,J. Reduction of caveolin 1 gene expression in lung carcinoma cell lines, Bioc- hem.Biophys.Res.Commun., 255: 580-586, 1999.
15 Schlott,T., Eiffert,H., Bohne,W., Landgrebe,J., Brunner,E., Spielbauer,B. and Knight,B. Chlamydia trachomatis modulates expression of tumor suppressor gene caveolin-1 and oncogene C-myc in the transformation zone of nonneo- plastic cervical tissue, Gynecol.Oncol., 98: 409-419, 2005.
16 Chan,T.F., Su,T.H., Yeh,K.T., Chang,J.Y., Lin,T.H., Chen,J.C., Yuang,S.S. and Chang,J.G. Mutational, epigenetic and expressional analyses of caveolin-1 gene in cervical cancers, Int.J.Oncol., 23: 599-604, 2003.
17 Bender,F.C., Reymond,M.A., Bron,C. and Quest,A.F. Caveolin-1 levels are do- wnregulated in human colon tumors, and ectopic expression of caveolin-1 in colon carcinoma cell lines reduces cell tumorigenicity, Cancer Res., 60: 5870- 5878, 2000.
18 Tirado,O.M., Mateo-Lozano,S., Villar,J., Dettin,L.E., Llort,A., Gallego,S., Ban, J., Kovar,H. and Notario,V. Caveolin-1 (CAV1) is a target of EWS/FLI-1 and a key determinant of the oncogenic phenotype and tumorigenicity of Ewing's sarcoma cells, Cancer Res., 66: 9937-9947, 2006.
19 Karam,J.A., Lotan,Y., Roehrborn,C.G., Ashfaq,R., Karakiewicz,P.I. and Shariat, S.F. Caveolin-1 overexpression is associated with aggressive prostate cancer recurrence, Prostate, 67: 614-622, 2007.
20 Joo,H.J., Oh,D.K., Kim,Y.S., Lee,K.B. and Kim,S.J. Increased expression of caveolin-1 and microvessel density correlates with metastasis and poor prog- nosis in clear cell renal cell carcinoma, BJU.Int., 93: 291-296, 2004.
21 Cormack,B.P., Valdivia,R.H. and Falkow,S. FACS-optimized mutants of the green fluorescent protein (GFP), Gene, 173: 33-38, 1996.
1 Fiucci,G., Ravid,D., Reich,R. and Liscovitch,M. Caveolin-1 inhibits anchorage- independent growth, anoikis and invasiveness in MCF-7 human breast cancer cells, Oncogene, 21: 2365-2375, 2002.
2 Lee,S.W., Reimer,C.L., Oh,P., Campbell,D.B. and Schnitzer,J.E. Tumor cell gro- wth inhibition by caveolin re-expression in human breast cancer cells, Onco- gene, 16: 1391-1397, 1998.
3 Cox,A.D. and Der,C.J. Biological assays for cellular transformation, Methods Enzymol., 238: 277-294, 1994.
4 Koleske,A.J., Baltimore,D. and Lisanti,M.P. Reduction of caveolin and caveolae in oncogenically transformed cells, Proc.Natl.Acad.Sci.U.S.A, 92: 1381-1385, 1995.
5 Sloan,E.K., Stanley,K.L. and Anderson,R.L. Caveolin-1 inhibits breast cancer growth and metastasis, Oncogene, 23: 7893-7897, 2004.
6 Hino,M., Doihara,H., Kobayashi,K., Aoe,M. and Shimizu,N. Caveolin-1 as tum- or suppressor gene in breast cancer, Surg.Today, 33: 486-490, 2003.
7 Fiucci,G., Ravid,D., Reich,R. and Liscovitch,M. Caveolin-1 inhibits anchorage- independent growth, anoikis and invasiveness in MCF-7 human breast cancer cells, Oncogene, 21: 2365-2375, 2002.
8 Belanger,M.M., Roussel,E. and Couet,J. Caveolin-1 is down-regulated in human lung carcinoma and acts as a candidate tumor suppressor gene, Chest, 125: 106S, 2004.
9 Racine,C., Belanger,M., Hirabayashi,H., Boucher,M., Chakir,J. and Couet,J. Reduction of caveolin 1 gene expression in lung carcinoma cell lines, Biochem. Biophys.Res.Commun., 255: 580-586, 1999.
10 Chan,T.F., Su,T.H., Yeh,K.T., Chang,J.Y., Lin,T.H., Chen,J.C., Yuang,S.S. and Chang,J.G. Mutational, epigenetic and expressional analyses of caveolin-1 gene in cervical cancers, Int.J.Oncol., 23: 599-604, 2003.
11 Wiechen,K., Diatchenko,L., Agoulnik,A., Scharff,K.M., Schober,H., Arlt,K., Zhumabayeva,B., Siebert,P.D., Dietel,M., Schafer,R. and Sers,C. Caveolin-1 is down-regulated in human ovarian carcinoma and acts as a candidate tumor sup- pressor gene, Am.J.Pathol., 159: 1635-1643, 2001.
12 Patlolla,J.M., Swamy,M.V., Raju,J. and Rao,C.V. Overexpression of caveolin-1in experimental colon adenocarcinomas and human colon cancer cell lines, Oncol.Rep., 11: 957-963, 2004.
13 Zhang,H., Su,L., Muller,S., Tighiouart,M., Xu,Z., Zhang,X., Shin,H.J., Hunt,J., Sun,S.Y., Shin,D.M. and Chen,Z.G. Restoration of caveolin-1 expression sup- presses growth and metastasis of head and neck squamous cell carcinoma, Br.J.Cancer, 99: 1684-1694, 2008.
14 Bender,F.C., Reymond,M.A., Bron,C. and Quest,A.F. Caveolin-1 levels are down-regulated in human colon tumors, and ectopic expression of caveolin-1 in colon carcinoma cell lines reduces cell tumorigenicity, Cancer Res., 60: 5870- 5878, 2000.
15 Sotgia,F., Del,G.F., Casimiro,M.C., Bonuccelli,G., Mercier,I., Whitaker-Menezes,D., Daumer,K.M., Zhou,J., Wang,C., Katiyar,S., Xu,H., Bosco,E., Quong,A.A., Aronow,B., Witkiewicz,A.K., Minetti,C., Frank,P.G., Jimenez,S.A., Knudsen, E.S., Pestell,R.G. and Lisanti,M.P. Caveolin-1-/- null mammary stromal fibrob- lasts share characteristics with human breast cancer-associated fibroblasts, Am.J.Pathol., 174: 746-761, 2009.
16 Sagara,Y., Mimori,K., Yoshinaga,K., Tanaka,F., Nishida,K., Ohno,S., Inoue,H. and Mori,M. Clinical significance of Caveolin-1, Caveolin-2 and HER2/neu mRNA expression in human breast cancer, Br.J.Cancer, 91: 959-965, 2004.
17 Zhou,H., Jia,L., Wang,S., Wang,H., Chu,H., Hu,Y., Cao,J. and Zhang,J. Diverge- nt expression and roles for caveolin-1 in mouse hepatocarcinoma cell lines with varying invasive ability, Biochem.Biophys.Res.Commun., 345: 486-494, 2006.
18 Kim,D.H. and Rossi,J.J. Strategies for silencing human disease using RNA interference, Nat.Rev.Genet., 8: 173-184, 2007.
19 Rana,T.M. Illuminating the silence: understanding the structure and function of small RNAs, Nat.Rev.Mol.Cell Biol., 8: 23-36, 2007.
20 Rossi,J.J. Realizing the promise of RNAi, Mol.Ther., 16: 810-811, 2008.
1 Williams,T.M. and Lisanti,M.P. Caveolin-1 in oncogenic transformation, cancer, and metastasis, Am.J.Physiol Cell Physiol, 288: C494-C506, 2005.
2 Liu,J., Lee,P., Galbiati,F., Kitsis,R.N. and Lisanti,M.P. Caveolin-1 expression sensitizes fibroblastic and epithelial cells to apoptotic stimulation, Am.J. Physiol Cell Physiol, 280: C823-C835, 2001.
3 Liu,J., Lee,P., Galbiati,F., Kitsis,R.N. and Lisanti,M.P. Caveolin-1 expression sensitizes fibroblastic and epithelial cells to apoptotic stimulation, Am.J. Physiol Cell Physiol, 280: C823-C835, 2001.
4 Ingueneau,C., Huynh-Do,U., Thiers,J.C., Negre-Salvayre,A., Salvayre,R. and Vindis,C. Caveolin-1 sensitizes vascular smooth muscle cells to mildly oxidized LDL-induced apoptosis, Biochem.Biophys.Res.Commun., 369: 889-893, 2008.
5 Timme,T.L., Goltsov,A., Tahir,S., Li,L., Wang,J., Ren,C., Johnston,R.N. and Thompson,T.C. Caveolin-1 is regulated by c-myc and suppresses c-myc-induced apoptosis, Oncogene, 19: 3256-3265, 2000.
6 Tso,C.L., McBride,W.H., Sun,J., Patel,B., Tsui,K.H., Paik,S.H., Gitlitz,B., Caliliw,R., van,O.A., Wu,L., deKernion,J. and Belldegrun,A. Androgen depr- ivation induces selective outgrowth of aggressive hormone-refractory prostate cancer clones expressing distinct cellular and molecular properties not present in parental androgen-dependent cancer cells, Cancer J., 6: 220-233, 2000.
7 Li,L., Ren,C.H., Tahir,S.A., Ren,C. and Thompson,T.C. Caveolin-1 maintains activated Akt in prostate cancer cells through scaffolding domain binding site interactions with and inhibition of serine/threonine protein phosphatases PP1 and PP2A, Mol.Cell Biol., 23: 9389-9404, 2003.
8 Li,L., Yang,G., Ebara,S., Satoh,T., Nasu,Y., Timme,T.L., Ren,C., Wang,J., Tahir, S.A. and Thompson,T.C. Caveolin-1 mediates testosterone-stimulated survival/ clonal growth and promotes metastatic activities in prostate cancer cells, Cancer Res., 61: 4386-4392, 2001.
9 Nasu,Y., Timme,T.L., Yang,G., Bangma,C.H., Li,L., Ren,C., Park,S.H., DeLeon, M., Wang,J. and Thompson,T.C. Suppression of caveolin expression induces androgen sensitivity in metastatic androgen-insensitive mouse prostate cancer cells, Nat.Med., 4: 1062-1064, 1998.
10 Wang,M.J., Liu,S., Liu,Y. and Zheng,D. Actinomycin D enhances TRAIL-induced caspase-dependent and -independent apoptosis in SH-SY5Y neuro- blastoma cells, Neurosci.Res., 59: 40-46, 2007.
11 Glazyrin,A.L., Chinni,S., Alhasan,S., Adsay,V.N., Vaitkevicius,V.K. and Sarkar, F.H. Molecular mechanism(s) of actinomycin-D induced sensitization of pan- creatic cancer cells to CD95 mediated apoptosis, Int.J.Oncol., 20: 201-205, 2002.
12 Kleeff,J., Kornmann,M., Sawhney,H. and Korc,M. Actinomycin D induces apo- ptosis and inhibits growth of pancreatic cancer cells, Int.J.Cancer, 86: 399-407, 2000.
13 Zundel,W., Swiersz,L.M. and Giaccia,A. Caveolin 1-mediated regulation of re- ceptor tyrosine kinase-associated phosphatidylinositol 3-kinase activity by ceramide, Mol.Cell Biol., 20: 1507-1514, 2000.
14 Altieri,D.C. Survivin, versatile modulation of cell division and apoptosis in cancer, Oncogene, 22: 8581-8589, 2003.
15 Fornaro,M., Plescia,J., Chheang,S., Tallini,G., Zhu,Y.M., King,M., Altieri,D.C. and Languino,L.R. Fibronectin protects prostate cancer cells from tumor ne- crosis factor-alpha-induced apoptosis via the AKT/survivin pathway, J.Biol. Chem., 278: 50402-50411, 2003.
1 Hakomori,S. Tumor malignancy defined by aberrant glycosylation and sphingo(glyco)lipid metabolism, Cancer Res., 56: 5309-5318, 1996.
2 Wang,L., Liang,Y., Li,Z., Cai,X., Zhang,W., Wu,G., Jin,J., Fang,Z., Yang,Y. and Zha,X. Increase in beta1-6 GlcNAc branching caused by N-acety-lglucosaminyltransferase V directs integrin beta1 stability in human hepatocellular carcinoma cell line SMMC-7721, J.Cell Biochem., 100: 230-241, 2007.
3 Dennis,J.W., Laferte,S., Waghorne,C., Breitman,M.L. and Kerbel,R.S. Beta 1-6 branching of Asn-linked oligosaccharides is directly associated with metastasis, Science, 236: 582-585, 1987.
4 Wang,S., Jia,L., Zhou,H., Wang,X. and Zhang,J. Caveolin-1 promotes the transformation and anti-apoptotic ability of mouse hepatoma cells, IUBMB.Life, 60: 693-699, 2008.
5 Nabeshima,K., Iwasaki,H., Koga,K., Hojo,H., Suzumiya,J. and Kikuchi,M. Emmprin (basigin/CD147): matrix metalloproteinase modulator and multifunctional cell recognition molecule that plays a critical role in cancer progression, Pathol.Int., 56: 359-367, 2006.
6 Yan,L., Zucker,S. and Toole,B.P. Roles of the multifunctional glycoprotein, emmprin (basigin; CD147), in tumour progression, Thromb.Haemost., 93: 199-204, 2005.
7 Muramatsu,T. and Miyauchi,T. Basigin (CD147): a multifunctional transmem- brane protein involved in reproduction, neural function, inflammation and tumor invasion, Histol.Histopathol., 18: 981-987, 2003.
8 Jia,L., Wang,S., Zhou,H., Cao,J., Hu,Y. and Zhang,J. Caveolin-1 up-regulates CD147 glycosylation and the invasive capability of murine hepatocarcinoma cell lines, Int.J.Biochem.Cell Biol., 38: 1584-1593, 2006.
9 Wang,L., Liang,Y., Li,Z., Cai,X., Zhang,W., Wu,G., Jin,J., Fang,Z., Yang,Y. and Zha,X. Increase in beta1-6 GlcNAc branching caused by N-acetylglucosaminyltransferase V directs integrin beta1 stability in human hepatocellular carcinoma cell line SMMC-7721, J.Cell Biochem., 100: 230-241, 2007.
10 Duffy,M.J., McGowan,P.M. and Gallagher,W.M. Cancer invasion and metastasis: changing views, J.Pathol., 214: 283-293, 2008.
11 Price,J.T. and Thompson,E.W. Mechanisms of tumour invasion and metastasis:emerging targets for therapy, Expert.Opin.Ther.Targets., 6: 217-233, 2002.
12 Williams,T.M. and Lisanti,M.P. Caveolin-1 in oncogenic transformation, cancer, and metastasis, Am.J.Physiol Cell Physiol, 288: C494-C506, 2005.
13 Freeze,H.H. Lectin affinity chromatography, Curr.Protoc.Protein Sci., Chapter 9: Unit, 2001.
14 Habermaas,S. and Spiess,E. Cell surface glycosylation and characterization of a differentially expressed glycoprotein in metastatic and non metastatic cell lines of the rat BSp73 tumor, Anticancer Res., 12: 1251-1258, 1992.
15 Kobata,A. Altered glycosylation of surface glycoproteins in tumor cells and its clinical application, Pigment Cell Res., 2: 304-308, 1989.
16 Yagel,S., Feinmesser,R., Waghorne,C., Lala,P.K., Breitman,M.L. and Dennis,J.W. Evidence that beta 1-6 branched Asn-linked oligosaccharides on metastatic tumor cells facilitate invasion of basement membranes, Int.J.Cancer, 44: 685-690, 1989.
17 Reddy,B.V. and Kalraiya,R.D. Sialilated beta1,6 branched N-oligosaccharides modulate adhesion, chemotaxis and motility of melanoma cells: Effect on invasion and spontaneous metastasis properties, Biochim.Biophys.Acta, 1760: 1393-1402, 2006.
18 Seberger,P.J. and Chaney,W.G. Control of metastasis by Asn-linked, beta1-6 branched oligosaccharides in mouse mammary cancer cells, Glycobiology, 9: 235-241, 1999.
19 Lu,Y., Pelling,J.C. and Chaney,W.G. Tumor cell surface beta 1-6 branched oligosaccharides and lung metastasis, Clin.Exp.Metastasis, 12: 47-54, 1994.
20 Liu,B., Lin,Y. and Yin,H. [Inhibition effect of Swainsonine on the growth and metastasis of gastric cancer in vivo], Zhonghua Zhong.Liu Za Zhi., 20: 168-170, 1998.
21 Newton,S.A., White,S.L., Humphries,M.J. and Olden,K. Swainsonine inhibition of spontaneous metastasis, J.Natl.Cancer Inst., 81: 1024-1028, 1989.
22 Dennis,J.W. Effects of swainsonine and polyinosinic:polycytidylic acid on murine tumor cell growth and metastasis, Cancer Res., 46: 5131-5136, 1986.
23 Xu,J., Xu,H.Y., Zhang,Q., Song,F., Jiang,J.L., Yang,X.M., Mi,L., Wen,N., Tian,R., Wang,L., Yao,H., Feng,Q., Zhang,Y., Xing,J.L., Zhu,P. and Chen,Z.N. HAb18G/CD147 functions in invasion and metastasis of hepatocellular carcinoma, Mol.Cancer Res., 5: 605-614, 2007.
24 Tang,W., Chang,S.B. and Hemler,M.E. Links between CD147 function, glycosylation, and caveolin-1, Mol.Biol.Cell, 15: 4043-4050, 2004.
25 Yang,X., Tang,J., Rogler,C.E. and Stanley,P. Reduced hepatocyte proliferation is the basis of retarded liver tumor progression and liver regeneration in mice lacking N-acetylglucosaminyltransferaseⅢ, Cancer Res., 63: 7753-7759, 2003.
26 Yang,X., Bhaumik,M., Bhattacharyya,R., Gong,S., Rogler,C.E. and Stanley,P. New evidence for an extra-hepatic role of N-acetylglucosaminyltransferaseⅢin the progression of diethylnitrosamine-induced liver tumors in mice, Cancer Res., 60: 3313-3319, 2000.
27 Guo,P., Chen,H.J., Wang,Q.Y. and Chen,H.L. Down regulation of N-acetylglu- cosaminyltransferase V facilitates all-transretinoic acid to induce apoptosis of human hepatocarcinoma cells, Mol.Cell Biochem., 284: 103-110, 2006.
28 Guo,H.B., Liu,F. and Chen,H.L. Increased susceptibility to apoptosis of human hepatocarcinoma cells transfected with antisense N-acetylglucosaminyltransfe- rase V cDNA, Biochem.Biophys.Res.Commun., 264: 509-517, 1999.
29 Sasai,K., Ikeda,Y., Ihara,H., Honke,K. and Taniguchi,N. Caveolin-1 regulates the functional localization of N-acetylglucosaminyltransferaseⅢwithin the golgi apparatus, J.Biol.Chem., 278: 25295-25301, 2003.