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/cm² 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.

中文翻译：

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自噬调节 FSS 诱导的肝细胞癌细胞上皮间质转化

肝细胞癌是一种高度致命的疾病，严重威胁着人类的健康。流体剪切应力 (FSS) 是由异常通透性肿瘤血管中的血浆泄漏和淋巴引流不足引起的，已被确定为在病理上导致癌症转移。据报道，自噬和上皮间质转化（EMT）都参与了癌细胞的迁移和侵袭，但在肿瘤机械微环境下自噬和 EMT 之间的相互作用却鲜为人知。在这里，我们确定暴露于 1.4 达因/厘米²FSS可促进自噬体的形成，显着增加HepG2和QGY-7703细胞自噬相关标志物beclin1和ATG7的表达，以及LC3Ⅱ/Ⅰ的比值。FSS 负荷还升高了间充质标志物 N-钙粘蛋白、波形蛋白、Twist、Snail 和 β-连环蛋白的水平，而上皮标志物 E-钙粘蛋白显示出减少。一旦自噬被 3-甲基腺嘌呤 (3-MA) 阻断或敲低 ATG5，根据 E-cadherin、N-cadherin 和 β-catenin 的表达和易位，FSS 诱导的 EMT 的发生被显着抑制。鉴于 EMT 对细胞迁移的影响，我们观察到自噬的抑制可能会阻碍 FSS 诱导的细胞迁移。总的来说，