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

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-beta) 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- beta are bypassed during liver tumorigenesis via multiple mechanisms. Furthermore, along with malignant progression, TGF-beta switches to promote cancer cell survival and proliferation. This dichotomous nature of TGF-beta 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-beta signaling or restore its tumor-suppressive arm. This review summarizes how TGF-beta inhibits or promotes liver cancer cell survival and proliferation, highlighting the functional switch mechanisms during the process. Copyright (C) 2020, The Authors. Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Limited and Science Press.