Autocrine hepatocyte growth factor/scatter factor-Met signaling induces transformation and the invasive/metastastic phenotype in C127 cells

Oncogene. 1996 Aug 15;13(4):853-6.


Hepatocyte growth factor/scatter factor (HGF/SF) is a pleiotropic effector of cells expressing the Met tyrosine kinase receptor. C127 is a non-tumorigenic mouse cell line which expresses negligible levels of HGF/SF and Met proteins. In the present report we have generated C127 cells which overexpress HGF/SF and/or Met proteins, and have analysed the effect of HGF/SF-Met signaling in these cells. We show that this signaling pathway stimulates the growth and invasiveness of C127 cells in vitro and that cells overexpressing both HGF/SF and Met proteins (but neither alone) are phenotypically transformed and highly tumorigenic and metastatic in vivo. Our data unequivocally demonstrates the autocrine dependency of HGF/SF-Met-induced transformation and metastasis in this system and supports the theory that the inappropriate expression of HGF/SF and Met proteins could play a role in the development and spread of human tumors. In addition, this system may be useful for identifying metastasis-associated genes that are activated by HGF/SF-Met signaling.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Line
  • Cell Transformation, Neoplastic / genetics
  • Female
  • Hepatocyte Growth Factor / metabolism*
  • Humans
  • Mice
  • Mice, Nude
  • Neoplasm Invasiveness / genetics
  • Neoplasm Metastasis / genetics
  • Phenotype
  • Proto-Oncogene Proteins c-met
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Signal Transduction*


  • Hepatocyte Growth Factor
  • Proto-Oncogene Proteins c-met
  • Receptor Protein-Tyrosine Kinases