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Zyxin promotes hepatocellular carcinoma progression via the activation of AKT/mTOR signaling pathway

TIANYING CAI1,2, JUNJIE BAI1, PENG TAN3, ZHIWEI HUANG1, CHEN LIU1, ZIMING WU1, YONGLANG CHENG1, TONGXI LI1, YIFAN CHEN1, JIAN RUAN4, LIN GAO5, YICHAO DU3,*, WENGUANG FU1,3,*

1 Department of Hepatobiliary Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China
2 Biobank, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China
3 Academician (Expert) Workstation of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China
4 Department of Medical Oncology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310000, China
5 Department of Health Management, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China

* Corresponding Authors: YICHAO DU. Email: email; WENGUANG FU. Email: email

Oncology Research 2023, 31(5), 805-817. https://doi.org/10.32604/or.2023.029549

Abstract

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.

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APA Style
CAI, T., BAI, J., TAN, P., HUANG, Z., LIU, C. et al. (2023). Zyxin promotes hepatocellular carcinoma progression via the activation of akt/mtor signaling pathway. Oncology Research, 31(5), 805-817. https://doi.org/10.32604/or.2023.029549
Vancouver Style
CAI T, BAI J, TAN P, HUANG Z, LIU C, WU Z, et al. Zyxin promotes hepatocellular carcinoma progression via the activation of akt/mtor signaling pathway. Oncol Res. 2023;31(5):805-817 https://doi.org/10.32604/or.2023.029549
IEEE Style
T. CAI et al., "Zyxin promotes hepatocellular carcinoma progression via the activation of AKT/mTOR signaling pathway," Oncol. Res., vol. 31, no. 5, pp. 805-817. 2023. https://doi.org/10.32604/or.2023.029549



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