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Cancers 2017, 9(4), 39;

Hepatocyte Growth Factor/c-Met Signaling in Head and Neck Cancer and Implications for Treatment

Department of Pharmacology & Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15213, USA
University of Pittsburgh Cancer Center, Pittsburgh, PA 15213, USA
Author to whom correspondence should be addressed.
Academic Editor: Jill Siegfried
Received: 6 March 2017 / Revised: 14 April 2017 / Accepted: 20 April 2017 / Published: 24 April 2017
(This article belongs to the Special Issue Hepatocyte Growth Factor Pathway in Cancer)
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Aberrant signaling of the hepatocyte growth factor (HGF)/c-Met pathway has been identified as a promoter of tumorigenesis in several tumor types including head and neck squamous cell carcinoma (HNSCC). Despite a relatively low c-Met mutation frequency, overexpression of HGF and its receptor c-Met has been observed in more than 80% of HNSCC tumors, with preclinical and clinical studies linking overexpression with cellular proliferation, invasion, migration, and poor prognosis. c-Met is activated by HGF through a paracrine mechanism to promote cellular morphogenesis enabling cells to acquire mesenchymal phenotypes in part through the epithelial-mesenchymal transition, contributing to metastasis. The HGF/c-Met pathway may also act as a resistance mechanism against epidermal growth factor receptor (EGFR) inhibition in advanced HNSCC. Furthermore, with the identification of a biologically distinct subset of HNSCC tumors acquired from human papillomavirus (HPV) infection that generally portends a good prognosis, high expression of HGF or c-Met in HPV-negative tumors has been associated with worse prognosis. Dysregulated HGF/c-Met signaling results in an aggressive HNSCC phenotype which has led to clinical investigations for targeted inhibition of this pathway. In this review, HGF/c-Met signaling, pathway alterations, associations with clinical outcomes, and preclinical and clinical therapeutic strategies for targeting HGF/c-Met signaling in HNSCC are discussed. View Full-Text
Keywords: head and neck squamous cell carcinoma; HGF; c-Met; EMT; HPV; targeted therapies head and neck squamous cell carcinoma; HGF; c-Met; EMT; HPV; targeted therapies

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Rothenberger, N.J.; Stabile, L.P. Hepatocyte Growth Factor/c-Met Signaling in Head and Neck Cancer and Implications for Treatment. Cancers 2017, 9, 39.

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