Integrin Signaling and Cell Spreading Mediated by Phorbol 12-Myristate 13-Acetate Treatment

Abstract

Spreading of SNU16mAd gastric carcinoma cells was previously shown to be regulated via a signaling network from transforming growth factor b1 (TGFb1) to integrins signaling, through a mediation of protein kinase Cd(PKCd). However, in the previous study, the roles of PKCd appeared complicated. In this study to clarify the roles of PKCd in the spreading of the gastric carcinoma cells, we questioned if PKC activation via phorbol 12-myristate 13-acetate (PMA) treatment could mimic the TGFb1 effects. An acute PMA treatment increased phosphorylations of focal adhesion (FA) kinase, paxillin, c-Src, and cofilin, just as TGFb1 did. Furthermore, cell spreading mediated by TGFb1- or acute PMA treatment correlated with activation of RhoA, which regulates actin reorganization and FA formation. However, stress fiber formation was prominent in TGFb1-treated cells, compared to cortical actin organization in PMA-treated cells. Altogether, these observations indicate that acute PMA treatment could mimic the TGFb1 mechanisms for cell spreading through subtly different effects on actin reorganization.