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Volume 47 Issue 9
Sep.  2020
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Article Navigation >  Journal of Genetics and Genomics  > 2020  >  47(9): 497-512

The dichotomous role of TGF-β in controlling liver cancer cell survival and proliferation

doi: 10.1016/j.jgg.2020.09.005
  • a 

    Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Nanchang University, Nanchang, 330006, China

  • b 

    School of Biological Engineering, Huainan Normal University, Huainan, 232001, China

  • c 

    School of Basic Medical Sciences, Nanchang University, Nanchang 330006, China

  • d 

    Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China

  • e 

    Institute of Biomedical Sciences, Nanchang University Medical College, Nanchang, 330031, China

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    Abstract
  • Hepatocellular carcinoma (HCC) is the major form of primary liver cancer and one of the most prevalent and life-threatening malignancies globally. One of the hallmarks in HCC is the sustained cell survival and proliferative signals, which are determined by the balance between oncogenes and tumor suppressors. Transforming growth factor beta (TGF-β) is an effective growth inhibitor of epithelial cells including hepatocytes, through induction of cell cycle arrest, apoptosis, cellular senescence, or autophagy. The antitumorigenic effects of TGF-β are bypassed during liver tumorigenesis via multiple mechanisms. Furthermore, along with malignant progression, TGF-β switches to promote cancer cell survival and proliferation. This dichotomous nature of TGF-β is one of the barriers to therapeutic targeting in liver cancer. Thereafter, understanding the underlying molecular mechanisms is a prerequisite for discovering novel antitumor drugs that may specifically disable the growth-promoting branch of TGF-β signaling or restore its tumor-suppressive arm. This review summarizes how TGF-β inhibits or promotes liver cancer cell survival and proliferation, highlighting the functional switch mechanisms during the process.
    • These authors contributed equally to the work.
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