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

Rothenberger, Natalie and Stabile, Laura (2017) Hepatocyte Growth Factor/c-Met Signaling in Head and Neck Cancer and Implications for Treatment. Cancers, 9 (4). ISSN 2072-6694

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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.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Rothenberger, Natalie
Date: 24 April 2017
Date Type: Publication
Journal or Publication Title: Cancers
Volume: 9
Number: 4
Publisher: MDPI AG
DOI or Unique Handle: 10.3390/cancers9040039
Schools and Programs: School of Medicine > Pharmacology and Chemical Biology
Refereed: Yes
Uncontrolled Keywords: head and neck squamous cell carcinoma, HGF, c-Met, EMT, HPV, targeted therapies
ISSN: 2072-6694
Official URL:
Article Type: Review
Date Deposited: 19 Jan 2021 16:51
Last Modified: 19 Jan 2021 16:51


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