Glycochenodeoxycholate promotes hepatocellular carcinoma invasion and migration by AMPK/mTOR dependent autophagy activation. (10th July 2019)

• Record Type: Journal Article
• Authors: Gao, Lu; Lv, Gang; Li, Rong; Liu, Wen-ting; Zong, Chen; Ye, Fei; Li, Xiao-yong; Yang, Xue; Jiang, Jing-hua; Hou, Xiao-juan; Jing, Ying-ying; Han, Zhi-peng; Wei, Li-xin
• Is Part Of: Cancer letters. Volume 454(2019)
• Page Start: 215
• Page End: 223
• Publication Date: 2019-07-10
• Subjects: Hepatocellular carcinoma -- Cholestasis -- Metastasis -- Autophagy; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2019.04.009
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: Metastasis and recurrence severely impact the treatment effect of hepatocellular carcinoma (HCC). HCC complicated with cholestasis is more prone to recurrence and metastasis. Previous studies have implicated pathogenesis of HCC by bile acid; however, the underlying mechanism is unknown yet. Glycochenodeoxycholate (GCDC) is one of most important component of bile acid (BA). In the present study, the role of GCDC in HCC cells invasion was detected by in vitro and in vivo assays. GCDC was found to significantly enhance the invasive potential of HCC cells; Further studies showed that GCDC could induce autophagy activation and higher invasive capability in HCC cells. Interestingly, inhibition of autophagy by chloroquine (CQ) reversed this phenomenon. Subsequently, the correlation between TBA expression level and clinicopathological characteristics was analyzed in HCC patients. Clinically, high TBA level in HCC tissue was found to be associated with more invasive and poor survival in HCC patients. Mechanistic study showed that bile acid induced autophagy by targeting the AMPK/mTOR pathway in HCC cells. Therefore, our results suggest that bile acid may promote HCC invasion via activation of autophagy and the level of bile acid may serve as a potential useful indicator for prognosis of HCC patients. Highlights: GCDC enhanced the metastasis of HCC which was mediated by autophagy. AMPK/mTOR pathway contributed to the metastatic potential of HCC cells mediated by autophagy. TBA level was correlated to autophagy activation and HCC prognosis in clinically specimens.