MET activates STAT3

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R-HSA-8875791
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Pathway
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Homo sapiens
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The STAT3 transcription factor binds to activated MET through phosphorylated tyrosine residue Y1356 of MET. STAT3 may also bind to activated MET indirectly through GAB1, but this interaction has not been studied in detail. Activated MET induces phosphorylation of STAT3 at Y705, triggering STAT3 dimerization and nuclear translocation (Schaper et al. 1997, Boccaccio et al. 1998, Zhang et al. 2002, Cramer et al. 2005). Endocytosis of MET and interaction with STAT3 at endosomes may be required for sustained STAT3 phosphorylation in response to HGF stimulation (Kermorgant and Parker 2008). Activated SRC may also contribute to phosphorylation of STAT3 at Y705. STAT3 may promote HGF transcription in a SRC-dependent way, but this autocrine HGF loop may be limited to breast cancer cells (Wojcik et al. 2006, Sam et al. 2007). MET-mediated activation of STAT3 is implicated in anchorage independent cell growth and invasiveness downstream of HGF (Zhang et al. 2002, Cramer et al. 2005). MET can also interact with STAT1A, STAT1B and STAT5, but the biological importance of these interactions is not known (Runge et al. 1999).

Literature References
PubMed ID Title Journal Year
15838885 Activation of the c-Met receptor complex in fibroblasts drives invasive cell behavior by signaling through transcription factor STAT3

Cramer, A, Kleiner, S, Westermann, M, Meissner, A, Lange, A, Friedrich, K

J. Cell. Biochem. 2005
18779368 Receptor trafficking controls weak signal delivery: a strategy used by c-Met for STAT3 nuclear accumulation

Kermorgant, S, Parker, PJ

J. Cell Biol. 2008
9440692 Induction of epithelial tubules by growth factor HGF depends on the STAT pathway

Boccaccio, C, Andò, M, Tamagnone, L, Bardelli, A, Michieli, P, Battistini, C, Comoglio, PM

Nature 1998
11803465 Requirement of Stat3 signaling for HGF/SF-Met mediated tumorigenesis

Zhang, YW, Wang, LM, Jove, R, Vande Woude, GF

Oncogene 2002
9094433 Hepatocyte growth factor/scatter factor (HGF/SF) signals via the STAT3/APRF transcription factor in human hepatoma cells and hepatocytes

Schaper, F, Siewert, E, Gómez-Lechon, MJ, Gatsios, P, Sachs, M, Birchmeier, W, Heinrich, PC, Castell, J

FEBS Lett. 1997
10558875 STAT 1alpha/1beta, STAT 3 and STAT 5: expression and association with c-MET and EGF-receptor in long-term cultures of human hepatocytes

Runge, DM, Runge, D, Foth, H, Strom, SC, Michalopoulos, GK

Biochem. Biophys. Res. Commun. 1999
16407846 A novel activating function of c-Src and Stat3 on HGF transcription in mammary carcinoma cells

Wojcik, EJ, Sharifpoor, S, Miller, NA, Wright, TG, Watering, R, Tremblay, EA, Swan, K, Mueller, CR, Elliott, BE

Oncogene 2006
17967179 A novel activating role of SRC and STAT3 on HGF transcription in human breast cancer cells

Sam, MR, Elliott, BE, Mueller, CR

Mol. Cancer 2007
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