四跨膜蛋白CD151调节结直肠癌Notch相关信号通路的研究
|
摘要
[目的]研究CD151在结直肠癌Notch信号通路中的调节作用。[方法]通过Logrank (Mantel-Cox)分析TCGA数据库中CD151与结直肠癌患者生存期的关系,应用Western blot和实时定量聚合酶链反应(qRT-PCR)检测40例结直肠癌及癌旁组织以及慢病毒低表达CD151的HT29细胞株中Notch-1、Hes-1和Jagged-1的蛋白和mRNA的表达。[结果]通过分析TCGA数据库的数据得出CD151高表达的结直肠癌患者的2000d之内生存期明显低于CD151低表达的患者。在结直肠癌患者组织中CD151、Notch-1、Hes-1和Jagged-1的蛋白和mRNA的表达均高于癌旁组织(P均<0.05)。在敲低CD151的HT29-CD151-KD人结肠癌细胞株中,Notch-1、Hes-1和Jagged-1的蛋白和mRNA的表达明显降低(P均<0.05)。[结论] CD151表达情况影响结直肠癌患者的生存期,CD151可明显下调结直肠癌Notch相关信号通路。
[Purpose] To investigate the role of CD151 in Notch signal pathway of colorectal cancer.[Methods] The relationship between CD151 and survival of colorectal cancer patients in TCGA database was analyzed by Log-rank(Mantel-Cox) analysis. The expressions of CD151,Notch-1,Hes-1 and Jagged-1 proteins and mRNAs in 40 cases of colorectal cancer and CD151 knockdown human colon cancer HT29 cells were detected by qRT-PCR and Western blot methods. [Results] As the analysis of data from the TCGA database shown,the survival of colorectal cancer patients with high expression of CD151 were significantly lower than the survival of patients with low expression of CD151 within 2000 d. The expressions of CD151,Notch-1,Hes-1 and Jagged-1 proteins and mRNAs in colorectal cancer tissues were higher than those in cancer adjacent tissues(P<0.05). The expressions of Notch-1,Hes-1 and Jagged-1 proteins and mRNAs were decreased in CD151 knockdown HT29 cells compared with HT29 cells(P<0.05). [Conclusion] High expression of CD151 can significantly reduce the survival of patients with colorectal cancer,and CD151 significantly down-regulates the Notch signal pathway in colorectal cancer.
[Purpose] To investigate the role of CD151 in Notch signal pathway of colorectal cancer.[Methods] The relationship between CD151 and survival of colorectal cancer patients in TCGA database was analyzed by Log-rank(Mantel-Cox) analysis. The expressions of CD151,Notch-1,Hes-1 and Jagged-1 proteins and mRNAs in 40 cases of colorectal cancer and CD151 knockdown human colon cancer HT29 cells were detected by qRT-PCR and Western blot methods. [Results] As the analysis of data from the TCGA database shown,the survival of colorectal cancer patients with high expression of CD151 were significantly lower than the survival of patients with low expression of CD151 within 2000 d. The expressions of CD151,Notch-1,Hes-1 and Jagged-1 proteins and mRNAs in colorectal cancer tissues were higher than those in cancer adjacent tissues(P<0.05). The expressions of Notch-1,Hes-1 and Jagged-1 proteins and mRNAs were decreased in CD151 knockdown HT29 cells compared with HT29 cells(P<0.05). [Conclusion] High expression of CD151 can significantly reduce the survival of patients with colorectal cancer,and CD151 significantly down-regulates the Notch signal pathway in colorectal cancer.
引文
[1] Ricci-Vitiani L,Lombardi DG,Pilozzi E,et al. Identification and expansion of human colon-cancer-initiating cells[J].Nature,2007,445(7123):111-115.
[2] Zeng P,Wang YH,Si M,et al. Tetraspanin CD151 as an emerging potential poor prognostic factor across solid tumors:a systematic review and meta-analysis[J]. Oncotarget,2017,8(3):5592-5602
[3] Baldwin LA,Hoff JT,Lefringhouse J,et al. CD151-α3β1integrin complexes suppress ovarian tumor growth by repressing slug-mediated EMT and canonical Wnt signaling[J].Oncotarget,2014,5(23):12203-12217.
[4] Zhang F,Michaelson JE,Moshiach S,et al. Tetraspanin CD151 maintains vascular stability by balancing the forces of cell adhesion and cytoskeletal tension[J]. Blood,2011,118:4274-4284.
[5] Previs RA,Coleman RL,Harris AL,et al. Molecular pathways:translational and therapeutic implications of the notch signaling pathway in cancer[J]. Clin Cancer Res,2015,21(5):955-961.
[6] Dufraine J,Funahashi Y,Kitajewski J.Notch signaling regulates tumor angiogenesis by diverse mechanisms[J].Oncogene,2008,27(38):5132-5137.
[7] Kathleen M. Capaccione KM,Pine SR. The Notch signaling pathway as a mediator of tumor survival[J]. Carcinogenesis,2013,34(7):1420-1430.
[8] Zhang F,Michaelson JE,Moshiach S,et al. Tetraspanin CD151 maintains vascular stability by balancing the forces of cell adhesion and cytoskeletal tension[J]. Blood,2011,118:4274-4284.
[9] Lin PC,Lin SC,Lee CT,et al. Dynamic change of tetraspanin CD151 membrane protein expression in colorectal cancer patients[J]. Cancer Invest,2011,29(8):542-547.
[10] Chien CW,Lin SC,Lai YY,et al. Regulation of CD151 by hypoxia controls cell adhesion and metastasis in colorectal cancer[J]. Clin Cancer Res,2008,14(24):8043-8051.
[2] Zeng P,Wang YH,Si M,et al. Tetraspanin CD151 as an emerging potential poor prognostic factor across solid tumors:a systematic review and meta-analysis[J]. Oncotarget,2017,8(3):5592-5602
[3] Baldwin LA,Hoff JT,Lefringhouse J,et al. CD151-α3β1integrin complexes suppress ovarian tumor growth by repressing slug-mediated EMT and canonical Wnt signaling[J].Oncotarget,2014,5(23):12203-12217.
[4] Zhang F,Michaelson JE,Moshiach S,et al. Tetraspanin CD151 maintains vascular stability by balancing the forces of cell adhesion and cytoskeletal tension[J]. Blood,2011,118:4274-4284.
[5] Previs RA,Coleman RL,Harris AL,et al. Molecular pathways:translational and therapeutic implications of the notch signaling pathway in cancer[J]. Clin Cancer Res,2015,21(5):955-961.
[6] Dufraine J,Funahashi Y,Kitajewski J.Notch signaling regulates tumor angiogenesis by diverse mechanisms[J].Oncogene,2008,27(38):5132-5137.
[7] Kathleen M. Capaccione KM,Pine SR. The Notch signaling pathway as a mediator of tumor survival[J]. Carcinogenesis,2013,34(7):1420-1430.
[8] Zhang F,Michaelson JE,Moshiach S,et al. Tetraspanin CD151 maintains vascular stability by balancing the forces of cell adhesion and cytoskeletal tension[J]. Blood,2011,118:4274-4284.
[9] Lin PC,Lin SC,Lee CT,et al. Dynamic change of tetraspanin CD151 membrane protein expression in colorectal cancer patients[J]. Cancer Invest,2011,29(8):542-547.
[10] Chien CW,Lin SC,Lai YY,et al. Regulation of CD151 by hypoxia controls cell adhesion and metastasis in colorectal cancer[J]. Clin Cancer Res,2008,14(24):8043-8051.