αvβ6-Fyn Signaling Promotes Oral Cancer Progression

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.