Anti-FYN monoclonal antibody, clone FQS6611

The 5-year survival rate for patients with oral cancer remains at 50%, in large part due the high rate of post-treatment recurrence. In this study, we transfected epithelial-specific integrin alpha v beta 6 and Fyn-kinase, a member of the Src-family kinases, into embryonic murine fibroblasts. In oral cancer, expression of alpha v beta 6 is neo-expressed. Using a variety of in vitro assays, including cell migration and multicellular spheroid formation, we determined that these embryonic fibroblasts expressing alpha v beta 6 and Fyn-kinase were able to acquire an epithelial phenotype. This is in direct contrast to human oral SCC, where expression of alpha v beta 6 with Fyn-kinase promotes epithelial to mesenchymal transition. This demonstrates that signaling pathways can be species-specific.

Wnt ligands signal through canonical or non-canonical signaling pathways. Although both routes share common elements, such as the Fz2 receptor, they differ in the co-receptor and in many of the final responses; for instance, whereas canonical Wnts increase beta-catenin stability, non-canonical ligands downregulate it. However, both types of ligands stimulate tumor cell invasion. We show here that both the canonical Wnt3a and the non-canonical Wnt5a stimulate Fz2 tyrosine phosphorylation, Fyn binding to Fz2, Fyn activation and Fyn-dependent Stat3 phosphorylation. Wnt3a and Wnt5a require Src for Fz2 tyrosine phosphorylation; Src binds to canonical and non-canonical co-receptors (LRP5/6 and Ror2, respectively) and is activated by Wnt3a and Wnt5a. This Fz2/Fyn/Stat3 branch is incompatible with the classical Fz2/Dvl2 pathway as shown by experiments of over-expression or depletion. Fyn is necessary for transcription of genes associated with invasiveness, such as Snail1, and for activation of cell invasion by both Wnt ligands. Our results extend the knowledge about canonical Wnt pathways, demonstrating additional roles for Fyn in this pathway and describing how this protein kinase is activated by both canonical and non-canonical Wnts.