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Fluid Shear Stress Promotes Autophagy in Hepatocellular Carcinoma Cells

机译:流体剪切应力促进肝癌细胞中的自噬。

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The autophagy in cancer cells is recognized as an essential hallmark of tumors, which can enhance cancer cell migration and invasion, and result in high incidence of tumor metastasis. The fluid shear stress (FSS) in tumor mechanical microenvironment plays a pivotal role in mediating the behaviors and functions of cells. In this study, the hepatocellular carcinoma cells were exposed to 1.4 dyn/cm2 FSS to explore whether FSS could induce autophagy. The results of TEM, Ad-mCherry-GFP labeled LC3B, and mRNA and protein expression of autophagy markers confirmed that FSS could induce autophagy in a time-dependent manner. Additionally, the inhibition of autophagy significantly downregulated the expression of PI3K, FAK and Rho GTPases, and attenuated the ability of cell migration, suggesting that FSS-induced autophagy depended on PI3K- FAK-Rho GTPases pathway. This study elucidated the role of FSS in inducing autophagy during tumor progression, which has emerged as a promising clinical strategy for cancer.
机译:癌细胞中的自噬被认为是肿瘤的重要标志,可以增强癌细胞的迁移和侵袭,并导致肿瘤转移的高发生率。肿瘤机械微环境中的流体剪切应力(FSS)在介导细胞行为和功能中起着关键作用。在这项研究中,肝细胞癌细胞暴露于1.4 dyn / cm2 FSS,以研究FSS是否可以诱导自噬。 TEM,Ad-mCherry-GFP标记的LC3B以及自噬标记的mRNA和蛋白表达的结果证实FSS可以以时间依赖性方式诱导自噬。此外,自噬的抑制作用显着下调了PI3K,FAK和Rho GTPases的表达,并减弱了细胞迁移的能力,这表明FSS诱导的自噬依赖于PI3K-FAK-Rho GTPases途径。这项研究阐明了FSS在肿瘤进展过程中诱导自噬的作用,这已成为一种有希望的癌症临床策略。

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