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

Gautam Maulik, Amol Shrikhande, Takashi Kijima, Patrick C. Ma, Paul T. Morrison, Ravi Salgia

Research output: Contribution to journalReview articlepeer-review

350 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)41-59
Number of pages19
JournalCytokine and Growth Factor Reviews
Volume13
Issue number1
DOIs
StatePublished - May 6 2002

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Immunology and Allergy
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)

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