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Papers In Press, published online ahead of print May 6, 2002
Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI 48109
Corresponding Author: cunywang{at}umich.edu
Hepatocyte growth factor (HGF), also known as a scatter factor, regulates a variety of biological activities including cell proliferation, survival, migration, and angiogenesis. Importantly, HGF and its receptor c-Met have been found to be associated with metastasis of human head and neck squamous cell carcinoma (HNSCC). Since anoikis resistance plays an important role in tumor progression and metastasis, here we examined whether HGF suppressed suspension-induced apoptosis (anoikis) in HNSCC cells, and if so, assessed downstream signaling pathways mediated by HGF. We found that HNSCC cells underwent anoikis upon loss of matrix contact, whereas HGF provided protection against it. HGF-induced anoikis resistance was found to be dependent on both ERK and Akt signaling pathways. Inhibition of either ERK or Akt activation abolished HGF-mediated survival. Furthermore, we found that HGF did not activate NF-kB transcription in HNSCC cells and that HGF-mediated anoikis resistance was independent of NF-kB. Taken together, our results suggest that anoikis resistance induced by HGF may also play an important role in the progression and metastasis of HNSCC.
J. Biol. Chem, 10.1074/jbc.M201598200
Submitted on February 15, 2002
Revised on April 16, 2002
Accepted on May 6, 2002
Hepatocyte growth factor inhibits anoikis in head and neck squamous cell carcinoma cells by activation of ERK and Akt signaling independent of NF-
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