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Met signaling:
Targeting tumor cell growth and invasion

Met activation occurs following binding of its ligand, hepatocyte growth factor (HGF), also known as scatter factor (SF).1,2 Upon activation, the intracellular domain of Met recruits a variety of proteins to trigger multiple signaling pathways.1,2 Met activation in tumor cells may lead to:

  • Stimulation of uncontrolled cell proliferation1,2
  • Promotion of cell survival under environmental/therapeutic stress1,2
  • Modification of cell-cell adhesion and induction of motility and invasion1,2
MET Pathway
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Met signaling can lead to invasive cancer growth.1,2 Met is primarily activated through binding of its ligand, hepatocyte growth factor (HGF), also known as scatter factor (SF).1,2 Met and/or HGF/SF expression in a variety of tumor types correlates with worse prognosis.1,2 Met signaling can be enhanced in tumor cells through overexpression of Met (with or without gene amplification), mutations in the gene encoding MET, and/or increased levels of active HGF/SF.1,2

Met is a cell surface receptor tyrosine kinase that requires receptor pairing in order to function. Met activation occurs following binding of its ligand, hepatocyte growth factor (HGF), also known as scatter factor (SF).3 Once activated, the intracellular domains of Met recruit a variety of signaling proteins, such as PI3K, a kinase that drives tumor cell survival signals, and Gab1 and Grb2, signaling adaptors that further amplify and transmit signals leading to cellular proliferation and migration in preclinical models.4,5

Met signaling in tumor cells may lead to6-8

  • Increased/uncontrolled cell proliferation
  • Angiogenesis
  • Metastasis
  • Resistance to
    • Apoptosis (programmed cell death)
    • Chemotherapy, radiotherapy, and targeted therapies
References:
1.
Birchmeier C, Birchmeier W, Gherardi E, Vande Woude GF. Met, metastasis, motility and more. Nat Rev Mol Cell Biol. 2003;4:915-925.
2.
Abounader R, Laterra J. Scatter factor/hepatocyte growth factor in brain tumor growth and angiogenesis. Neuro Oncol. 2005;7:436-451.