αvβ6-Fyn Signaling Promotes Oral Cancer Progression

Xiaowu Li, Yongjian Yang, Yongmei Hu, Dongmin Dang, Joseph Regezi, Brian L. Schmidt, Amha Atakilit, Bing Chen, Duncan Ellis, Daniel M. Ramos

Research output: Contribution to journalArticle

Abstract

We have previously shown that the integrin β6 is neoexpressed in invasive oral squamous cell carcinoma (SCC) and is correlated with oral tumor progression. However, the mechanism by which the integrin β6 promotes oral tumor progression is not well understood. The purpose of the present study was to determine whether integrin β 6 signaling activates Fyn and thus promotes oral squamous cell carcinoma progression. We analyzed the integrin β6 signaling complex and investigated the function of these signaling molecules in oral SCC cells. We found that, upon ligation of the integrin β6 with fibronectin, β6 complexed with Fyn and activated it. The activation of Fyn recruited and activated focal adhesion kinase to this complex. This complex was necessary to activate Shc and to couple β6 signaling to the Raf-ERK/MAPK pathway. This pathway transcriptionally activated the matrix metalloproteinase-3 gene and promoted oral SCC cell proliferation and experimental metastasis in vivo. These findings indicate that integrin β6 signaling activates Fyn and thus promotes oral cancer progression.

Original languageEnglish (US)
Pages (from-to)41646-41653
Number of pages8
JournalJournal of Biological Chemistry
Volume278
Issue number43
DOIs
StatePublished - Oct 24 2003

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Li, X., Yang, Y., Hu, Y., Dang, D., Regezi, J., Schmidt, B. L., Atakilit, A., Chen, B., Ellis, D., & Ramos, D. M. (2003). αvβ6-Fyn Signaling Promotes Oral Cancer Progression. Journal of Biological Chemistry, 278(43), 41646-41653. https://doi.org/10.1074/jbc.M306274200