Transforming growth factor-beta1 suppresses hepatocellular carcinoma proliferation via activation of Hippo signaling

Oncotarget. 2017 May 2;8(18):29785-29794. doi: 10.18632/oncotarget.14523.

Abstract

In this study, we examined the expression of core proteins of the Hippo signaling pathway in hepatocellular carcinoma (HCC) cells treated with transforming growth factor-β 1(TGF-β1) and investigated the relationship between TGF-β1 and the Hippo signaling pathway, in order to better understand their roles in HCC and their potential implications for cancer therapy. We prove that the Hippo signaling pathway is involved in the TGF-β1-induced inhibition of the growth of HCC cells. Large tumor suppressor expression (LATS1) was overexpression and yes association protein 1(YAP1) translocated from the nucleus to the cytoplasm in HCC cells treated with TGF-β1. Overexpression of LATS1 and the nucleocytoplasmic translocation of YAP1 play an anti-oncogenetic role in the occurrence and development of liver cancer. Our findings provide new insight into strategies for liver cancer therapy.

Keywords: Hippo signaling; hepatocellular carcinoma; proliferation; transforming growth factor-beta.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Apoptosis / drug effects
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Gene Expression
  • Hippo Signaling Pathway
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Protein Serine-Threonine Kinases / metabolism*
  • Protein Transport
  • Signal Transduction / drug effects*
  • Transcription Factors
  • Transforming Growth Factor beta1 / pharmacology*
  • YAP-Signaling Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • Phosphoproteins
  • Transcription Factors
  • Transforming Growth Factor beta1
  • YAP-Signaling Proteins
  • YAP1 protein, human
  • Protein Serine-Threonine Kinases