αvβ6-Fyn Signaling Promotes Oral Cancer Progression

Abstract

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

Gene-Expression Profile Changes Correlated with Tumor Progression and Lymph Node Metastasis in Esophageal Cancer

“…Among them, for instance, integrin ␣5 is known to activate signal transduction, enhance cell proliferation, suppress apoptosis, and thereby contribute to tumor progression in lung squamous cell carcinoma (30). ITGB6 also promotes the progression of oral squamous cell carcinoma by activating Fyn on binding to fibronectin (31), which showed higher expression in the progressed tumors in our study. Among cell death regulators, NOL3 inhibits apoptosis (32).…”

Budesonide exerts its chemopreventive efficacy during mouse lung tumorigenesis by modulating gene expressions

“…Cdc28 is the main CDK driving the cell cycle in budding yeast. Genetic interactions with checkpoint and APC mutants suggest Cdc28 may regulate checkpoint arrest downstream of the Budesonide-treated tumors also show decreased expression of the proto-oncogene Fyn, which is associated with tumor progression in cancer models including oral squamous cell carcinoma and metastatic murine melanoma (Huang et al, 2003;Li et al, 2003). This suggests a progressive phenotype for the It was recently reported that a combination treatment of dexamethasone and cisplatin on solid tumors of the lung and cervix resulted in less apoptosis compared with cisplatin alone (Herr et al, 2003).…”

RACK1-mediated Integration of Adhesion and Insulin-like Growth Factor I (IGF-I) Signaling and Cell Migration Are Defective in Cells Expressing an IGF-I Receptor Mutated at Tyrosines 1250 and 1251

“…There is much evidence to suggest an important role for RACK1 in regulating cell adhesion and motility/chemotaxis (32,(37)(38)(39). RACK1 has been shown to directly interact with ␤1 integrins (40).…”