α_vβ₆-Fyn Signaling Promotes Oral Cancer Progression

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.