1. Academic Validation
  2. Glycochenodeoxycholate promotes hepatocellular carcinoma invasion and migration by AMPK/mTOR dependent autophagy activation

Glycochenodeoxycholate promotes hepatocellular carcinoma invasion and migration by AMPK/mTOR dependent autophagy activation

  • Cancer Lett. 2019 Jul 10;454:215-223. doi: 10.1016/j.canlet.2019.04.009.
Lu Gao 1 Gang Lv 2 Rong Li 1 Wen-Ting Liu 1 Chen Zong 1 Fei Ye 1 Xiao-Yong Li 1 Xue Yang 1 Jing-Hua Jiang 1 Xiao-Juan Hou 1 Ying-Ying Jing 1 Zhi-Peng Han 3 Li-Xin Wei 4
Affiliations

Affiliations

  • 1 Tumor Immunology and Gene Therapy Center, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China.
  • 2 The 8th Medical Center of Chinese PLA General Hospital, Beijing, China.
  • 3 Tumor Immunology and Gene Therapy Center, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China. Electronic address: hanzhipeng0311@126.com.
  • 4 Tumor Immunology and Gene Therapy Center, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China. Electronic address: weilixin_smmu@163.com.
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.

Keywords

Autophagy; Cholestasis; Hepatocellular carcinoma; Metastasis.

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