Autophagy modulates FSS‐induced epithelial–mesenchymal transition in hepatocellular carcinoma cells. Issue 9 (9th June 2021)

• Record Type: Journal Article
• Authors: Su, Guanyue; Feng, Tang; Pei, Tong; Yang, Fan; Sun, Denglian; Yu, Hongchi; Wang, Xiaoli; Gao, Wenbo; He, Jia; Shen, Yang; Liu, Xiaoheng
• Is Part Of: Molecular carcinogenesis. Volume 60:Issue 9(2021)
• Page Start: 607
• Page End: 619
• Publication Date: 2021-06-09
• Subjects: autophagy -- cell migration -- epithelial–mesenchymal transition -- fluid shear stress; Carcinogenesis -- Molecular aspects -- Periodicals; 616.994071
• DOI: 10.1002/mc.23327
• Languages: English
• ISSNs: 0899-1987

Abstract

Abstract: Hepatocellular carcinoma is a highly fatal disease and threatens human health seriously. Fluid shear stress (FSS), which is caused by the leakage of plasma from abnormally permeable tumor blood vessels and insufficient lymphatic drainage, has been identified as contributing pathologically to cancer metastasis. Autophagy and epithelial–mesenchymal transition (EMT) are both reported to be involved in cancer cell migration and invasion, but little has been revealed about the interaction between autophagy and EMT under a tumor mechanical microenvironment. Here, we identified that exposure to 1.4 dyne/cm 2 FSS could promote the formation of autophagosomes and significantly increase the expressions of autophagy‐related markers of beclin1 and ATG7, and the ratio of LC3Ⅱ/Ⅰ in both of HepG2 and QGY‐7703 cells. The FSS loading also elevated the levels of mesenchymal markers N‐cadherin, Vimentin, Twist, Snail, and β‐catenin, while the epithelial markers E‐cadherin showed a decrease. Once the autophagy was blocked by 3‐methyladenine (3‐MA) or knocking ATG5 down, the occurrence of FSS‐induced EMT was inhibited dramatically according to the expression and translocation of E‐cadherin, N‐cadherin, and β‐catenin. Given the effect of EMT on cell migration, we observed that inhibition of autophagy could impede FSS‐induced cell migration. Collectively, this study demonstrated that autophagy played a crucial role in FSS‐induced EMT and cell migration in hepatocellular carcinoma.