Role of the hepatocyte growth factor receptor, c-Met, in oncogenesis and potential for therapeutic inhibition

Cytokine Growth Factor Rev. 2002 Feb;13(1):41-59. doi: 10.1016/s1359-6101(01)00029-6.


Receptor tyrosine kinases have become important therapeutic targets for anti-neoplastic molecularly targeted therapies. c-Met is a receptor tyrosine kinase shown to be over-expressed and mutated in a variety of malignancies. Stimulation of c-Met via its ligand hepatocyte growth factor also known as scatter factor (HGF/SF), leads to a plethora of biological and biochemical effects in the cell. There has been considerable knowledge gained on the role of c-Met-HGF/SF axis in normal and malignant cells. This review summarizes the structure of c-Met and HGF/SF and their family members. Since there are known mutations of c-Met in solid tumors, particularly in papillary renal cell carcinoma, we have summarized the various mutations and over-expression of c-Met known thus far. Stimulation of c-Met can lead to scattering, angiogenesis, proliferation, enhanced cell motility, invasion, and eventual metastasis. The biological functions altered by c-Met are quite unique and described in detail. Along with biological functions, various signal transduction pathways, including the cytoskeleton are altered with the activation of c-Met-HGF/SF loop. We have recently shown the phosphorylation of focal adhesion proteins, such as paxillin and p125FAK in response to c-Met stimulation in lung cancer cells, and this is detailed here. Finally, c-Met when mutated or over-expressed in malignant cells serves as an important therapeutic target and the most recent data in terms of inhibition of c-Met and downstream signal transduction pathways is summarized.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antineoplastic Agents / pharmacology
  • Cell Division
  • Cell Movement
  • Hepatocyte Growth Factor / metabolism
  • Humans
  • Ligands
  • Models, Biological
  • Molecular Sequence Data
  • Mutation
  • Neoplasms / metabolism*
  • Neoplasms / therapy*
  • Neovascularization, Pathologic
  • Phylogeny
  • Protein Binding
  • Proto-Oncogene Proteins c-met / physiology*
  • Reactive Oxygen Species
  • Sequence Homology, Amino Acid
  • Tumor Cells, Cultured


  • Antineoplastic Agents
  • Ligands
  • Reactive Oxygen Species
  • Hepatocyte Growth Factor
  • Proto-Oncogene Proteins c-met