Full-length Mst1 exhibits growth promoting function in human hepatocellular carcinoma cells

FEBS Lett. 2013 Mar 1;587(5):496-503. doi: 10.1016/j.febslet.2013.01.018. Epub 2013 Jan 21.

Abstract

The putative tumor suppressor Mst1, when cleaved to its 36kDa cleaved form, amplifies apoptotic signals. We found that Mst1 was predominantly expressed in its full-length form in 76% (17/25 cases) of hepatocellular carcinoma (HCC) tumors. Mst1 cleavage was basically absent in HCC cells. Ectopic full-length Mst1 expression increased the growth of HCC cells by 55-80% within 3days after transfection. Expression of exogenous NORE1B, a tumor suppressor commonly lost in HCC tumors (~56% of our cohort), was sufficient to suppress the growth promotion of full-length Mst1. Hence, Mst1 exhibits a growth promoting activity in HCC cells upon NORE1B downregulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Apoptosis
  • Apoptosis Regulatory Proteins
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Proliferation*
  • Cell Survival
  • DNA Mutational Analysis
  • Gene Expression
  • Gene Expression Regulation, Neoplastic
  • HEK293 Cells
  • Hepatocyte Growth Factor / genetics
  • Hepatocyte Growth Factor / metabolism
  • Hepatocyte Growth Factor / physiology*
  • Humans
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Molecular Weight
  • Monomeric GTP-Binding Proteins / genetics
  • Monomeric GTP-Binding Proteins / metabolism
  • Proteolysis
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins / physiology*
  • Up-Regulation

Substances

  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • Proto-Oncogene Proteins
  • RASSF5 protein, human
  • macrophage stimulating protein
  • Hepatocyte Growth Factor
  • Monomeric GTP-Binding Proteins