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 Ser473 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.
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Acknowledgments
This study was supported by The Foundation of Major International Cooperation Projects of The Science and Technology (2010DFB30300) and the National Natural Science Foundation of China (81272193), National Basic Research Program of China (2010CB833605).
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All authors declared no conflict of interest.
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Jiang, X., Wang, J., Zhang, K. et al. The role of CD29-ILK-Akt signaling-mediated epithelial–mesenchymal transition of liver epithelial cells and chemoresistance and radioresistance in hepatocellular carcinoma cells. Med Oncol 32, 141 (2015). https://doi.org/10.1007/s12032-015-0595-x
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DOI: https://doi.org/10.1007/s12032-015-0595-x