title: The role of CD29-ILK-Akt signaling-mediated epithelial-mesenchymal transition of liver epithelial cells and chemoresistance and radioresistance in hepatocellular carcinoma cells.
abstract: Hepatocellular carcinomas (HCC) are aggressive cancers, and the prognosis of HCC patients is poor. This study investigated the roles of CD29 in epithelial-mesenchymal transition (EMT) and chemoresistance and radioresistance in HCC tumors. CD29 expression in HCC and peritumoral tissues was measured by immunohistochemistry. CD29 overexpression was established by an adenovirus-carrying CD29 gene expression cassette, while silencing of CD29 expression was established by an adenovirus-carrying shRNA. Western blot was used to measure protein expression, and MTT was used to analyze cell viability. Xenograft HCC mouse model was established by inoculating isolated CD29(+) and CD29(-) HCC tumor cells. Significantly higher percentage of positive CD29 expression was observed in HCC tissues compared to peritumoral tissues. Xenograft CD29(+) tumors grew more quickly than CD29(-) tumors. CD29(+) tumors were more resistant to radiotherapy and cisplatin therapy than CD29(-) tumors. Overexpression of CD29 significantly increased the resistance of CD29(-) tumors to radiation and cisplatin treatment. In contrast, silencing of CD29 expression significantly sensitized CD29(+) tumors to irradiation and cisplatin treatment. Overexpression of CD29 decreased E-cadherin, but increased fibronectin, vimentin, ILK activity, Akt Ser(473) phosphorylation, and mTORC1 protein expression in Hep G2 and THLE-3 cells. Moreover, overexpression of CD29 significantly increased the resistance of Hep G2 and THLE-3 cells to starvation, radiation, and cisplatin treatments. This study suggests that CD29 plays a crucial role in the resistance of HCC to chemo/radiotherapy and EMT of liver epithelial cells.
authors: Xiangya Nursing School, Central South University, 172 Tongzipo Road, Changsha, 410013, Hunan, People's Republic of China, jxr7542@163.com.
authors: Xiaorong
authors: X
authors: Jiang
authors: Jingxia
authors: J
authors: Wang
authors: Kaili
authors: K
authors: Zhang
authors: Siyuan
authors: S
authors: Tang
authors: Caiping
authors: C
authors: Ren
authors: Yuxiang
authors: Y
authors: Chen
mesh_terms: D000818:Animals; D015820:Cadherins / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D056945:Hep G2 Cells; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D011836:Radiation Tolerance / Q000187:drug effects / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014746:Vimentin / Q000235:genetics; D000099200:Scaffold Protein ILK
chemical_list: D015820:Cadherins; D019012:Integrin beta1; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D014746:Vimentin; D000099200:Scaffold Protein ILK