S2046 Reducing Tumor Growth On Stents Using Nanorods: Nanotechnology for the Prevention of Cell Adhesion and Migration

Src activity might induce the recruitment of Dyn2, we first tested the role of the adaptor protein Grb2 which is known to bind to the proline-rich domain (PRD) of Dyn2 at the plasma membrane during endocytosis. Surprisingly, Grb2 was also recruited to FAs following Src activation, and knockdown of Grb2 inhibited Dyn2's FA targeting. To test if Src might activate Dyn2 to alter FA dynamics, we mutated specific Src substrates on Dyn2 to mimic either phosph-active Dyn2 (Dyn2 Y231, 597E), or phospho-defective Dyn2 (Dyn2 Y231, 597F). Interestingly, expression of the Dyn2 YE form greatly increased internalization of an FA component β1-integrin (compared to WT cells) that potentiated the neoplastic potential of these cells as they became substantially more rounded and poorly adherent with more dynamic FAs. Together, we conclude that Src kinase acts to regulate FA dynamics in two related but distinct ways; first, by increasing Dyn2 recruitment to adhesion sites via the Grb2 adaptor, and second, via phospho-activation of Dyn2 leading to increased endocytic turnover of FA components. These findings provide a novel mechanistic insight into how EGFR/Src signaling promotes pancreatic cancer cell migration and metastasis.