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 beta 1 (TGF beta 1) to integrins signaling, through a mediation of protein kinase C delta (PKC delta). However, in the previous study, the roles of PKC delta appeared complicated. In this study to clarify the roles of PKC delta in the spreading of the gastric carcinoma cells, we questioned if PKC activation via phorbol 12-myristate 13-acetate (PMA) treatment could mimic the TGF beta 1 effects. An acute PMA treatment increased phosphorylations of focal adhesion (FA) kinase, paxillin, c-Src, and cofilin, just as TGF beta 1 did. Furthermore, cell spreading mediated by TGF beta 1 - or acute PMA treatment correlated with activation of RhoA, which regulates actin reorganization and FA formation. However, stress fiber formation was prominent in TGF beta 1-treated cells, compared to cortical actin organization in PMA-treated cells. Altogether, these observations indicate that acute PMA treatment could mimic the TGF beta 1 mechanisms for cell spreading through subtly different effects on actin reorganization.