Escape from TGF-β-induced senescence promotes aggressive hallmarks in epithelial hepatocellular carcinoma cells.

ABSTRACT: Transforming growth factor-β (TGF-β) signaling and cellular senescence are key hallmarks of hepatocellular carcinoma (HCC) pathogenesis. Despite provoking senescence-associated growth arrest in epithelial HCC cells, elevated TGF-β activity paradoxically correlates with increased aggressiveness and poor prognosis in advanced tumors. Whether the transition between these dichotomous functions involves modulation of the senescence phenotype during disease progression remains elusive. Exploiting the epithelial HCC cell line Huh7 as a robust model, we demonstrate that chronic exposure to TGF-β prompts escape from Smad3-mediated senescence, leading to the development of TGF-β resistance. This altered state is characterized by an optimal proliferation rate and the acquisition of molecular and func

SUBMITTER: Kalyoncu M 

PROVIDER: S-EPMC12420363 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature