MET: a critical player in tumorigenesis and therapeutic target

Cold Spring Harb Perspect Biol. 2013 Jul 1;5(7):a009209. doi: 10.1101/cshperspect.a009209.


Since its discovery more than 25 years ago, numerous studies have established that the MET receptor is unique among tyrosine kinases. Signaling through MET is necessary for normal development and for the progression of a wide range of human cancers. MET activation has been shown to drive numerous signaling pathways; however, it is not clear how MET signaling mediates diverse cellular responses such as motility, invasion, growth, and angiogenesis. Great strides have been made in understanding the pleotropic aspects of MET signaling using three-dimensional molecular structures, cell culture systems, human tumors, and animal models. These combined approaches have driven the development of MET-targeted therapeutics that have shown promising results in the clinic. Here we examine the unique features of MET and hepatocyte growth factor/scatter factor (HGF/SF) structure and signaling, mutational activation, genetic mouse models of MET and HGF/SF, and MET-targeted therapeutics.

Publication types

  • Review

MeSH terms

  • Animals
  • Carcinogenesis*
  • Gene Expression Regulation, Neoplastic
  • Hepatocyte Growth Factor / metabolism
  • Humans
  • Mice
  • Models, Biological
  • Mutation
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins c-met / chemistry
  • Proto-Oncogene Proteins c-met / genetics
  • Proto-Oncogene Proteins c-met / physiology*
  • Signal Transduction


  • Hepatocyte Growth Factor
  • Proto-Oncogene Proteins c-met