肝细胞癌（HCC）是一种常见的恶性肿瘤，由多个基因和通路推动。本研究旨在探讨肝癌中肌动蛋白相互作用蛋白Zyxin（ZYX）的作用和特定机制。我们发现ZYX的表达在HCC组织中显著高于正常肝组织。此外，在肝细胞瘤细胞系（PLC/PRF/5, HCCLM3）中过表达ZYX能增强其增殖、迁移和侵袭，而ZYX的沉默则产生相反效应（SK HEP-1, Huh-7）。此外，ZYX表达水平的改变也影响与细胞周期、迁移和侵袭相关的蛋白的表达。Xenograft模型获得了类似的结果。AKT/mTOR信号通路是癌症发展的关键介导者之一。ZYX过表达上调磷酸化的AKT/mTOR蛋白水平，而其沉默则产生相反效应。此外，AKT抑制剂MK2206中和ZYX对HCC细胞的促癌作用，而AKT激活剂SC79恢复了ZYX沉默HCC细胞的增殖、迁移和侵袭能力。综上所述，ZYX通过激活AKT/mTOR信号通路促进了HCC的恶性进展，并且是HCC的潜在治疗靶点。© 2023 Cai et al.

Hepatocellular carcinoma (HCC) is a common malignancy that is driven by multiple genes and pathways. The aim of this study was to investigate the role and specific mechanism of the actin-interacting protein zyxin (ZYX) in HCC. We found that the expression of ZYX was significantly higher in HCC tissues compared to that in normal liver tissues. In addition, overexpression of ZYX in hepatoma cell lines (PLC/PRF/5, HCCLM3) enhanced their proliferation, migration and invasion, whereas ZYX knockdown had the opposite effects (SK HEP-1, Huh-7). Furthermore, the change in the expression levels of ZYX also altered that of proteins related to cell cycle, migration and invasion. Similar results were obtained with xenograft models. The AKT/mTOR signaling pathway is one of the key mediators of cancer development. While ZYX overexpression upregulated the levels of phosphorylated AKT/mTOR proteins, its knockdown had the opposite effect. In addition, the AKT inhibitor MK2206 neutralized the pro-oncogenic effects of ZYX on the HCC cells, whereas the AKT activator SC79 restored the proliferation, migration and invasion of HCC cells with ZYX knockdown. Taken together, ZYX promotes the malignant progression of HCC by activating AKT/mTOR signaling pathway, and is a potential therapeutic target in HCC.© 2023 Cai et al.