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Published on: October 13, 2019
Integrin signaling and cell spreading mediated by phorbol 12-myristate 13-acetate treatment
Mi-Sook Lee1, Yong-Bae Kim, Sung-Yul Lee
1Department of Molecular and Clinical Oncology, Cancer Research Institute, College of Medicine, Seoul National University, 28 Yeongeon-dong, Jongno-gu, Seoul 110-799, Korea.
Abstract:
Spreading of SNU16mAd gastric carcinoma cells was previously shown to be regulated via a signaling network from transforming growth factor beta1 (TGFbeta1) to integrins signaling, through a mediation of protein kinase C delta (PKCdelta). However, in the previous study, the roles of PKCdelta appeared complicated. In this study to clarify the roles of PKCdelta in the spreading of the gastric carcinoma cells, we questioned if PKC activation via phorbol 12-myristate 13-acetate (PMA) treatment could mimic the TGFbeta1 effects. An acute PMA treatment increased phosphorylations of focal adhesion (FA) kinase, paxillin, c-Src, and cofilin, just as TGFbeta1 did. Furthermore, cell spreading mediated by TGFbeta1- or acute PMA treatment correlated with activation of RhoA, which regulates actin reorganization and FA formation. However, stress fiber formation was prominent in TGFbeta1-treated cells, compared to cortical actin organization in PMA-treated cells. Altogether, these observations indicate that acute PMA treatment could mimic the TGFbeta1 mechanisms for cell spreading through subtly different effects on actin reorganization.
Insights
Phorbol 12-myristate 13-acetate (PMA) mimics transforming growth factor beta1 (TGFbeta1) in gastric cancer cell spreading by activating similar signaling pathways. However, PMA and TGFbeta1 induce distinct actin reorganization patterns, clarifying protein kinase C delta's complex role.
Area of Science:
- Cell Biology
- Molecular Oncology
- Signal Transduction
Background:
- Gastric carcinoma cell spreading is regulated by transforming growth factor beta1 (TGFbeta1) signaling.
- Protein kinase C delta (PKCdelta) mediates TGFbeta1 effects, but its role is complex.
- Investigating PKC activation to clarify its function in gastric cancer cell motility.
Purpose of the Study:
- To determine if phorbol 12-myristate 13-acetate (PMA) can mimic TGFbeta1-induced gastric carcinoma cell spreading.
- To elucidate the specific roles of PKCdelta in cell motility and actin dynamics.
Main Methods:
- Gastric carcinoma cells (SNU16mAd) treated with TGFbeta1 and PMA.
- Analysis of protein phosphorylation (FAK, paxillin, c-Src, cofilin).
- Assessment of RhoA activation and actin reorganization (stress fibers vs. cortical actin).
Main Results:
- Acute PMA treatment mimicked TGFbeta1 effects on cell spreading and RhoA activation.
- Both TGFbeta1 and PMA increased phosphorylation of key focal adhesion proteins.
- TGFbeta1 promoted stress fiber formation, while PMA induced cortical actin organization.
Conclusions:
- Acute PMA treatment partially mimics TGFbeta1-induced gastric cancer cell spreading via similar signaling pathways.
- Distinct actin reorganization patterns suggest differential downstream effects of PMA and TGFbeta1.
- Clarifies the complex role of PKCdelta in mediating cell motility and cytoskeletal dynamics.
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