Snail和E-cadherin在喉鳞癌中的表达与临床意义
|
摘要
随着对喉癌研究的深入,逐渐认识到淋巴结转移和肿瘤局部复发是影响喉癌预后的主要因素。如何提高喉癌转移的早期诊断水平是及时正确处理颈部转移病灶的关键,有益于提高临床生存率。
转录抑制因子Snail和上皮钙黏蛋白E-cadherin在上皮-间质转化(epithelial-esenchymal transition,EMT)过程中发挥着重要作用。Snail通过与E-cadherin启动子区的E-盒(E-box)结合,降低E-cadherin的表达进而诱导EMT的发生,从而促进肿瘤细胞从原发位置脱落,进而发生转移。国内外关于Snail和E-cadherin在肿瘤转移方面的研究,多致力于卵巢癌、结肠癌、食道癌等上皮性肿瘤的研究,尚未见两者在喉鳞癌方面的系统研究。本研究通过阐明Snail、E-cadherin在喉鳞癌、癌旁组织及息肉中的表达,来分析两者与喉鳞癌发生、发展的关系,并探讨Snail、E-cadherin在喉鳞癌中的表达与喉鳞癌患者临床病理各因素的关系,以及Snail、E-cadherin在喉鳞状细胞癌中表达的相关性。本实验通过免疫组织化学染色(S-P法)发现:Snail在喉鳞癌中的表达明显高于癌旁组织、声带息肉组织,而E-cadherin蛋白的表达与其相反;Snail的高表达与喉鳞癌的组织分化程度、颈淋巴结转移有关,E-cadherin表达的降低与喉鳞状细胞癌的组织分化程度、T分级、临床分期以及颈淋巴结转移有关;在喉鳞癌中Snail和E-cadherin的表达呈负相关,上述结果说明两者联合检测可作为喉鳞癌恶性程度和预后的参考指标,并可为个性化治疗提供参考信息。
Purpose:
To study the expression of Snail and E-cadherin in Laryngeal squamous cell carcinoma(LSCC)、normal squamous epidermis near cancer and polyp of vocal cord,and the relationship of the expression with the clinical pathology characteristics of LSCC, and also to understand the correlation between the expression of Snail and E-cadherin in LSCC.
Methods:
46 samples were cut off from surgical operations in the First Hospital of Jilin University from March 2008 to November 2009. 46 samples of normal squamous epidermis near cancer were selected, And 10 samples of polyp of vocal card were restored for contrast. The patients'age, sex, tumor position, T stage, clinical stage, differentiation and cervical lymph node matastasis were recorded. All samples were diagnosed by special pathologists. The pathological specimen was cut in the thickness of 4um. Streptavidin peroxidase(SP) immunohistochemistry staining for Snail and E-cadherin were made. The result of immunohistochemistry were determined by the intensity of staining and the number of positive cells. The expressions of Snail and E-cadherin in LSCC, normal squamous epidermis near cancer and polyp of vocal cord were analyzed. The relationship with the expression of Snail and E-cadherin with the clinical pathology characteristics were done. And the relevance of the expression of Snailand E-cadherin in LSCC was analyzed.
Result:
(1)The positive rate of Snail expression was 69.57%(32/46) in LSCC, in normal squamous epidermis near cancer was36.67%(17/46), and in polyp of vocal cord was 30.00%(3/10).The expression of Snail in LSCC was significantly higher than that in normal squamous epidermis near cancer and in polyp of vocal cord(P<0.05) . There was a significant correlation between the expression of Snail in LSCC with the differentiation and cervical lymph node matastasis (P<0.05).However There was no significant correlation between the expression of Snail with the patients'age, sex, tumor position, T stage , clinical stage(P>0.05).
(2)The positive rate of E-cadherin expression was47.83%(22/46)in LSCC, and in normal squamous epidermis near cancer was78.3%(36/46), and in polyp of vocal cord was 90.0%(9/10). The expression of E-cadherin in LSCC was significantly lower than that in normal squamous epidermis near cancer and in polyp of vocal cord(P<0.05). There was a significant correlation between the expression of E-cadherin in LSCC with the T stage, clinical stage, cervical lymph node matastasis and differentiation (P<0.05).while There was no significant correlation between the expression of E-cadherin with the patients'age, sex and tumor position(P>0.05).
(3)In LSCC, The expression of Snail was inversely correlated with expression of E-cadherin (r=-0.5690, P<0.01).
Conclusion:
(1)The expression of Snail was significantly increased in LSCC compared with in normal squamous epidermis near cancer and in polyp of vocal cord. Higher Snail expression was significantly associated with the differentiation and cervical lymph node matastasis (P<0.05). Higher Snail expression may imply more aggressive malignant behaviors of LSCC.
(2)The expression of E-cadherin was significantly reduced in LSCC compared with in normal squamous epidermis near cancer and in polyp of vocal cord. Descending E-cadherin expression was significantly associated with the T stage, clinical stage, cervical lymph node matastasis and differentiation (P<0.05).Descending E-cadherin expression may imply more aggressive malignant behaviors of LSCC.
(3)In LSCC, The expression of Snail and E-cadherin were negatively correlated.
转录抑制因子Snail和上皮钙黏蛋白E-cadherin在上皮-间质转化(epithelial-esenchymal transition,EMT)过程中发挥着重要作用。Snail通过与E-cadherin启动子区的E-盒(E-box)结合,降低E-cadherin的表达进而诱导EMT的发生,从而促进肿瘤细胞从原发位置脱落,进而发生转移。国内外关于Snail和E-cadherin在肿瘤转移方面的研究,多致力于卵巢癌、结肠癌、食道癌等上皮性肿瘤的研究,尚未见两者在喉鳞癌方面的系统研究。本研究通过阐明Snail、E-cadherin在喉鳞癌、癌旁组织及息肉中的表达,来分析两者与喉鳞癌发生、发展的关系,并探讨Snail、E-cadherin在喉鳞癌中的表达与喉鳞癌患者临床病理各因素的关系,以及Snail、E-cadherin在喉鳞状细胞癌中表达的相关性。本实验通过免疫组织化学染色(S-P法)发现:Snail在喉鳞癌中的表达明显高于癌旁组织、声带息肉组织,而E-cadherin蛋白的表达与其相反;Snail的高表达与喉鳞癌的组织分化程度、颈淋巴结转移有关,E-cadherin表达的降低与喉鳞状细胞癌的组织分化程度、T分级、临床分期以及颈淋巴结转移有关;在喉鳞癌中Snail和E-cadherin的表达呈负相关,上述结果说明两者联合检测可作为喉鳞癌恶性程度和预后的参考指标,并可为个性化治疗提供参考信息。
Purpose:
To study the expression of Snail and E-cadherin in Laryngeal squamous cell carcinoma(LSCC)、normal squamous epidermis near cancer and polyp of vocal cord,and the relationship of the expression with the clinical pathology characteristics of LSCC, and also to understand the correlation between the expression of Snail and E-cadherin in LSCC.
Methods:
46 samples were cut off from surgical operations in the First Hospital of Jilin University from March 2008 to November 2009. 46 samples of normal squamous epidermis near cancer were selected, And 10 samples of polyp of vocal card were restored for contrast. The patients'age, sex, tumor position, T stage, clinical stage, differentiation and cervical lymph node matastasis were recorded. All samples were diagnosed by special pathologists. The pathological specimen was cut in the thickness of 4um. Streptavidin peroxidase(SP) immunohistochemistry staining for Snail and E-cadherin were made. The result of immunohistochemistry were determined by the intensity of staining and the number of positive cells. The expressions of Snail and E-cadherin in LSCC, normal squamous epidermis near cancer and polyp of vocal cord were analyzed. The relationship with the expression of Snail and E-cadherin with the clinical pathology characteristics were done. And the relevance of the expression of Snailand E-cadherin in LSCC was analyzed.
Result:
(1)The positive rate of Snail expression was 69.57%(32/46) in LSCC, in normal squamous epidermis near cancer was36.67%(17/46), and in polyp of vocal cord was 30.00%(3/10).The expression of Snail in LSCC was significantly higher than that in normal squamous epidermis near cancer and in polyp of vocal cord(P<0.05) . There was a significant correlation between the expression of Snail in LSCC with the differentiation and cervical lymph node matastasis (P<0.05).However There was no significant correlation between the expression of Snail with the patients'age, sex, tumor position, T stage , clinical stage(P>0.05).
(2)The positive rate of E-cadherin expression was47.83%(22/46)in LSCC, and in normal squamous epidermis near cancer was78.3%(36/46), and in polyp of vocal cord was 90.0%(9/10). The expression of E-cadherin in LSCC was significantly lower than that in normal squamous epidermis near cancer and in polyp of vocal cord(P<0.05). There was a significant correlation between the expression of E-cadherin in LSCC with the T stage, clinical stage, cervical lymph node matastasis and differentiation (P<0.05).while There was no significant correlation between the expression of E-cadherin with the patients'age, sex and tumor position(P>0.05).
(3)In LSCC, The expression of Snail was inversely correlated with expression of E-cadherin (r=-0.5690, P<0.01).
Conclusion:
(1)The expression of Snail was significantly increased in LSCC compared with in normal squamous epidermis near cancer and in polyp of vocal cord. Higher Snail expression was significantly associated with the differentiation and cervical lymph node matastasis (P<0.05). Higher Snail expression may imply more aggressive malignant behaviors of LSCC.
(2)The expression of E-cadherin was significantly reduced in LSCC compared with in normal squamous epidermis near cancer and in polyp of vocal cord. Descending E-cadherin expression was significantly associated with the T stage, clinical stage, cervical lymph node matastasis and differentiation (P<0.05).Descending E-cadherin expression may imply more aggressive malignant behaviors of LSCC.
(3)In LSCC, The expression of Snail and E-cadherin were negatively correlated.
引文
[1]韩瑞珠,李晓丹,王鑫,等.凋亡相关基因在喉鳞状细胞癌中的表达概括[J].肿瘤, 2005, 25(4): 331-334.
[2] David Shook and Ray Keller. Mechanisms mechanics and function of epithelial- mesenchymal transitions in early development[J]. Mechanisms of Development, 2003, 120(11): 1351-1383.
[3] Brigitte Boyer, Ana Maria Valles and Nataeha Edme. Induction and regulation of epithelial-mesenehymal transitions[J]. Bioehemieal Pharma- eology, 2000, 60(8): 1091-1099.
[4] Ray M E, Mehra R, Sandler H M, et al. E-cadherin protein expression predicts prostate cancer salvage radiotherapy outcomes [J]. J Urology, 2006, 176(4): 1409-1414.
[5] Shapiro L, Fannon AM, Kwong PD, et al. Structural basis of cell-cell adhesion by cadesions[J].Nature, 1995, 374: 327-337.
[6] Larue L, Bellcosa A. Epithelial-mesenchymal transition in development and cancer: role lf phosphatidylinositol 3, kinase /AKT pathway [J]. Oncogene, 2005, 24, 7442-7454.
[7] Y Usam, S Satake, F Nakayama, et al. Snail-associated epithelial- mesenchymal transition promotes oesophageal squamous cell carcinoma motility and progression[J]. J Path, 2008, 215: 330-339.
[8] Come C, Arnoux V, Bibeau F, et al. Roles of the transcription factors snail and slug during mammary morphogenesis and breast carcinoma progression [J]. J Mammary Gland Biol Neoplasia, 2004, 9(2): 183-193.
[9] Rosivatz E, Becker I, Specht K, et al, Differential expression of the epithelial-mesenchymal transition regulators snail, SIPI, and twist in gastric camer [J]. Am J Pathol, 2002, 161(5): 1881-1891.
[10] Batlle E, Sancho E, Franci C, et al. The transcription factor Snail is a repressor of E-cadherin gene expression in epithelial tumor cells[J]. Nat Cell Biol, 2002, 2(2): 84-89.
[11] Palmer HG, LarribaMJ, Garcia JM1.The transcription factor SNAIL represses vitamin D receptor expression and responsiveness in human colon cancer [J]. Nat Med, 2004, 10(9): 917-919.
[12] Shook D, Keller R. Mechanisms, mechanics and function of epithelial- mesenchymal transitions in early development. Mech Dev, 2003, 120(11): 1351-1383.
[13] BoutetA. Esteban MA. Maxwell PH, et al. Reactivation of Snail genes in renal fibrosis and carcinomas: a process of reversed embryogenesis[J]. Cell Cycle, 2007, 6 (6): 638-642.
[14] Rodrigo I, Cato AC, Cano A. Regulation of E-cadherin gene expression during tumor progression: the role of a new Ets-binding site and the E-pal element.Exp Cell Res, 1999, 248(2): 358-371.
[15] Mirna A, Perez-Moreno’, MarioF. Regulation of tight punitions during the epithelium-mesenchyme transition: direct repression of the gene expression of claudins/occluding by Snail[J]. Joumal of Cell Science. 2003, 116: 499.
[16] Hugh TJ, Dillon SA, Taylor BA, et al. Cadherin-catenine expression in primary colorectal cancer: a survival analysis. Br J Cancer, 1999, 80: 1046-1051.
[17] M. Angela Nieto. The SLUG zinc - finger protein represses E -cadherin in breast cancer[J ].Nature Reviews/ Molecular Cell Biology, 2002, 3: 155.
[18] Nigam AK, PignatelliM, Boulos PB, et al. Current concepts in metastasis[J]1.Gut, 1994, 35: 996.
[19] Takeiehi M, Morphogenetic roles of classic cadherins[J]. Curr Opn Cell Biol, 1995, 7(5): 619-627.
[20] Yu J, Eberr MPA, Miehlke S, et al.α-catenin expression is decreased in human gastric cancers and in the gastric mucosa of first degree relatives. Gut, 2000, 46(5): 639-644.
[21] Thiery JP. Epithelial-mesenchymal transitions in development and pathologies [J]. Curr Opin Cell Biol, 2003, 15(6): 740-746.
[22] Yokoyama K, Kamata N, Fujimoto R, et al. Increased invasion and matricmetalloproteinase-2 expression by Snail-induced mesenchymal transition in squamous cell carcinomas. Int J Oncol, 2003, 22: 891-898.
[23] MiyoshiA, Kitajima Y, Sumi K, et al. Snail and SIP1 increase cancer invasion by up regulating MMP family in hepatocellular carcinoma cells[J]. Br J Cancer, 2004, 90(6): 1265-1273.
[24] Cho HJ, Baek KE, Saika S, et al. Snail is required for transforming growth factor-beta-induced epithelial-mesenchymal transition by activating PI3 kinase/Akt signal pathway. Biochem Biophys Res Commun, 2007, 353(2): 337-343.
[25] Huber MA, Kraut N, Beug H, et al. Molecular requirements for ep ithelial-mesenchymal transition during tumor progression [J].Curr Opin Cell Biol, 2005, 17: 548-558.
[26]金鸿雁,丰有吉.反义Snail转录因子抑制卵巢癌转移的实验研究.中华妇产科杂志, 2005, 40(6): 400-403.
[27]刘海,王志强.反义Snail转录因子抑制肝癌转移.世界华人消化杂志, 2006, 14(35): 3409-3413.
[28]陈丽,刘求真,邱际华等.人Sna il基因RNA i慢病毒载体对鼻咽癌5-8F细胞增殖和侵袭的影响.第三军医大学学报, 2009, 31(2): 1151-1154.
[29] Poser I, Dominguez D, de Herreros AG, et al. Loss of E-cadherin expression in melanoma cells involves up-regulation of the transcriptional repressor Snail. J Biol Chem, 2001, 276: 24661-24666.
[30] Yokoama K, Kamata N, Hayashi E, et al. Reverse correlation of E-cadherin and Snail expression in oral squamous cell carcinoma cells in vitro[J]. Oral Oncol 2001, 37: 65-71.
[31] Hongyan Jin, Yinhua Yu, Tao Zhang, et al. Snail is critical for tumor growth and metastasis of ovarian carcinoma[J]. Inter J Cancer 2009, 31: 41-72.
[32] Zhang A, Chen G, Meng L, et al. Antisense-Snail transfer inhibits tumor metastasis by inducing E-cadherin expression [J]. Anticancer Res, 2008, 28 (2A): 621-628.
[33] Olmeda D, Montes A, Moreno-Bueno G, et al. Snai1 and Snai2 collaborate on tumor growth and metastasis properties of mouse skin carcinoma cell lines[J]. Oncogene, 2008, 27(34): 4690-4701.
[34] Zeisberg M, Hanai J, Sugimoto H, et al. BMP-7 counteracts TGF-βinduced epithelial to mesenchymal transiton and reverses chronic renal injury. N at Med, 2003, 9(7): 964-968.
[35] Thiery, JP, Sleeman, J P. Complex networks orchestrate epithelial–mesenchymal transitions [J]. Nature Reviews Molecular Cell Biology, 2006, 7, 131-142.
[36] Nancy Gavert, Avri Ben-Ze’ev. Epithelial–mesenchymal transition and the invasive potential of tumors [J]. Trends in Molecular Medicine, 2008, 14(5): 199-209.
[37]张阿丽,王全胜,钟亚华,等.上皮性肿瘤细胞中Snail与E-cadherin的表达及其与体外侵袭性的关系[J].中华肿瘤杂志, 2006, 28(1): 17-20.
[38] Kuphal S, Poser I, Jobin C, et al. Loss of E-cadherin leads to upregulation of NFkappaB activity in malignant melanoma. Oncogene, 2004, 23(52): 8509-8519.
[39] Kuphal S, Bosserhoff AK. Influence of the cytoplasmic domain of E-cadherin on endogenous N-cadherin expression in malignant melanoma. Oncogene, 2006, 25(2):248-259.
[40] Nina Zidar , Nina Gale , Nika Kojc, et.al. Cadherin–catenin complex and transcription factor Snail-1 in spindle cell carcinoma of the head and neck[J]. Virchows Arch, 2008,453:267-274.
[41] Nika Kojc, Nina Zidar , Nina Gale, et.al. Transcription factors Snail, Slug, Twist, and SIP1 in spindle cell carcinoma of the head and neck [J]. Virchows Arch, 2009, 454: 549-555.
[42]张阿丽,王全胜,陈刚,等. Snail与E-cadherin在上皮性肿瘤中的表达及其临床意义[J].肿瘤, 2006, 26(5): 469-471.
[43]阎爱华,孙洋,王靖,等.宫颈鳞癌组织中SnailmRNA和蛋白的表达[J].郑州大学学报(医学版), 2008, 43(6): 1179-1183.
[44]陈澜涛,隋栋,徐世东,等. Snail与E-cadherin在食管癌中的表达及临床意义[J].中国医药指南, 2008, 6(2): 143-146.
[2] David Shook and Ray Keller. Mechanisms mechanics and function of epithelial- mesenchymal transitions in early development[J]. Mechanisms of Development, 2003, 120(11): 1351-1383.
[3] Brigitte Boyer, Ana Maria Valles and Nataeha Edme. Induction and regulation of epithelial-mesenehymal transitions[J]. Bioehemieal Pharma- eology, 2000, 60(8): 1091-1099.
[4] Ray M E, Mehra R, Sandler H M, et al. E-cadherin protein expression predicts prostate cancer salvage radiotherapy outcomes [J]. J Urology, 2006, 176(4): 1409-1414.
[5] Shapiro L, Fannon AM, Kwong PD, et al. Structural basis of cell-cell adhesion by cadesions[J].Nature, 1995, 374: 327-337.
[6] Larue L, Bellcosa A. Epithelial-mesenchymal transition in development and cancer: role lf phosphatidylinositol 3, kinase /AKT pathway [J]. Oncogene, 2005, 24, 7442-7454.
[7] Y Usam, S Satake, F Nakayama, et al. Snail-associated epithelial- mesenchymal transition promotes oesophageal squamous cell carcinoma motility and progression[J]. J Path, 2008, 215: 330-339.
[8] Come C, Arnoux V, Bibeau F, et al. Roles of the transcription factors snail and slug during mammary morphogenesis and breast carcinoma progression [J]. J Mammary Gland Biol Neoplasia, 2004, 9(2): 183-193.
[9] Rosivatz E, Becker I, Specht K, et al, Differential expression of the epithelial-mesenchymal transition regulators snail, SIPI, and twist in gastric camer [J]. Am J Pathol, 2002, 161(5): 1881-1891.
[10] Batlle E, Sancho E, Franci C, et al. The transcription factor Snail is a repressor of E-cadherin gene expression in epithelial tumor cells[J]. Nat Cell Biol, 2002, 2(2): 84-89.
[11] Palmer HG, LarribaMJ, Garcia JM1.The transcription factor SNAIL represses vitamin D receptor expression and responsiveness in human colon cancer [J]. Nat Med, 2004, 10(9): 917-919.
[12] Shook D, Keller R. Mechanisms, mechanics and function of epithelial- mesenchymal transitions in early development. Mech Dev, 2003, 120(11): 1351-1383.
[13] BoutetA. Esteban MA. Maxwell PH, et al. Reactivation of Snail genes in renal fibrosis and carcinomas: a process of reversed embryogenesis[J]. Cell Cycle, 2007, 6 (6): 638-642.
[14] Rodrigo I, Cato AC, Cano A. Regulation of E-cadherin gene expression during tumor progression: the role of a new Ets-binding site and the E-pal element.Exp Cell Res, 1999, 248(2): 358-371.
[15] Mirna A, Perez-Moreno’, MarioF. Regulation of tight punitions during the epithelium-mesenchyme transition: direct repression of the gene expression of claudins/occluding by Snail[J]. Joumal of Cell Science. 2003, 116: 499.
[16] Hugh TJ, Dillon SA, Taylor BA, et al. Cadherin-catenine expression in primary colorectal cancer: a survival analysis. Br J Cancer, 1999, 80: 1046-1051.
[17] M. Angela Nieto. The SLUG zinc - finger protein represses E -cadherin in breast cancer[J ].Nature Reviews/ Molecular Cell Biology, 2002, 3: 155.
[18] Nigam AK, PignatelliM, Boulos PB, et al. Current concepts in metastasis[J]1.Gut, 1994, 35: 996.
[19] Takeiehi M, Morphogenetic roles of classic cadherins[J]. Curr Opn Cell Biol, 1995, 7(5): 619-627.
[20] Yu J, Eberr MPA, Miehlke S, et al.α-catenin expression is decreased in human gastric cancers and in the gastric mucosa of first degree relatives. Gut, 2000, 46(5): 639-644.
[21] Thiery JP. Epithelial-mesenchymal transitions in development and pathologies [J]. Curr Opin Cell Biol, 2003, 15(6): 740-746.
[22] Yokoyama K, Kamata N, Fujimoto R, et al. Increased invasion and matricmetalloproteinase-2 expression by Snail-induced mesenchymal transition in squamous cell carcinomas. Int J Oncol, 2003, 22: 891-898.
[23] MiyoshiA, Kitajima Y, Sumi K, et al. Snail and SIP1 increase cancer invasion by up regulating MMP family in hepatocellular carcinoma cells[J]. Br J Cancer, 2004, 90(6): 1265-1273.
[24] Cho HJ, Baek KE, Saika S, et al. Snail is required for transforming growth factor-beta-induced epithelial-mesenchymal transition by activating PI3 kinase/Akt signal pathway. Biochem Biophys Res Commun, 2007, 353(2): 337-343.
[25] Huber MA, Kraut N, Beug H, et al. Molecular requirements for ep ithelial-mesenchymal transition during tumor progression [J].Curr Opin Cell Biol, 2005, 17: 548-558.
[26]金鸿雁,丰有吉.反义Snail转录因子抑制卵巢癌转移的实验研究.中华妇产科杂志, 2005, 40(6): 400-403.
[27]刘海,王志强.反义Snail转录因子抑制肝癌转移.世界华人消化杂志, 2006, 14(35): 3409-3413.
[28]陈丽,刘求真,邱际华等.人Sna il基因RNA i慢病毒载体对鼻咽癌5-8F细胞增殖和侵袭的影响.第三军医大学学报, 2009, 31(2): 1151-1154.
[29] Poser I, Dominguez D, de Herreros AG, et al. Loss of E-cadherin expression in melanoma cells involves up-regulation of the transcriptional repressor Snail. J Biol Chem, 2001, 276: 24661-24666.
[30] Yokoama K, Kamata N, Hayashi E, et al. Reverse correlation of E-cadherin and Snail expression in oral squamous cell carcinoma cells in vitro[J]. Oral Oncol 2001, 37: 65-71.
[31] Hongyan Jin, Yinhua Yu, Tao Zhang, et al. Snail is critical for tumor growth and metastasis of ovarian carcinoma[J]. Inter J Cancer 2009, 31: 41-72.
[32] Zhang A, Chen G, Meng L, et al. Antisense-Snail transfer inhibits tumor metastasis by inducing E-cadherin expression [J]. Anticancer Res, 2008, 28 (2A): 621-628.
[33] Olmeda D, Montes A, Moreno-Bueno G, et al. Snai1 and Snai2 collaborate on tumor growth and metastasis properties of mouse skin carcinoma cell lines[J]. Oncogene, 2008, 27(34): 4690-4701.
[34] Zeisberg M, Hanai J, Sugimoto H, et al. BMP-7 counteracts TGF-βinduced epithelial to mesenchymal transiton and reverses chronic renal injury. N at Med, 2003, 9(7): 964-968.
[35] Thiery, JP, Sleeman, J P. Complex networks orchestrate epithelial–mesenchymal transitions [J]. Nature Reviews Molecular Cell Biology, 2006, 7, 131-142.
[36] Nancy Gavert, Avri Ben-Ze’ev. Epithelial–mesenchymal transition and the invasive potential of tumors [J]. Trends in Molecular Medicine, 2008, 14(5): 199-209.
[37]张阿丽,王全胜,钟亚华,等.上皮性肿瘤细胞中Snail与E-cadherin的表达及其与体外侵袭性的关系[J].中华肿瘤杂志, 2006, 28(1): 17-20.
[38] Kuphal S, Poser I, Jobin C, et al. Loss of E-cadherin leads to upregulation of NFkappaB activity in malignant melanoma. Oncogene, 2004, 23(52): 8509-8519.
[39] Kuphal S, Bosserhoff AK. Influence of the cytoplasmic domain of E-cadherin on endogenous N-cadherin expression in malignant melanoma. Oncogene, 2006, 25(2):248-259.
[40] Nina Zidar , Nina Gale , Nika Kojc, et.al. Cadherin–catenin complex and transcription factor Snail-1 in spindle cell carcinoma of the head and neck[J]. Virchows Arch, 2008,453:267-274.
[41] Nika Kojc, Nina Zidar , Nina Gale, et.al. Transcription factors Snail, Slug, Twist, and SIP1 in spindle cell carcinoma of the head and neck [J]. Virchows Arch, 2009, 454: 549-555.
[42]张阿丽,王全胜,陈刚,等. Snail与E-cadherin在上皮性肿瘤中的表达及其临床意义[J].肿瘤, 2006, 26(5): 469-471.
[43]阎爱华,孙洋,王靖,等.宫颈鳞癌组织中SnailmRNA和蛋白的表达[J].郑州大学学报(医学版), 2008, 43(6): 1179-1183.
[44]陈澜涛,隋栋,徐世东,等. Snail与E-cadherin在食管癌中的表达及临床意义[J].中国医药指南, 2008, 6(2): 143-146.