ανβ6-Fyn signaling promotes oral cancer progression

We have previously shown that the integrin beta(6) is neo-expressed in invasive oral squamous cell carcinoma (SCC) and is correlated with oral tumor progression. However, the mechanism by which the integrin beta(6) promotes oral tumor progression is not well understood. The purpose of the present study was to determine whether integrin beta(6) signaling activates Fyn and thus promotes oral squamous cell carcinoma progression. We analyzed the integrin beta(6) signaling complex and investigated the function of these signaling molecules in oral SCC cells. We found that, upon ligation of the integrin beta(6) with fibronectin, beta(6) 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 beta6 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 beta(6) signaling activates Fyn and thus promotes oral cancer progression.