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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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CSK Tyrosine-Protein Kinase
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Carcinoma / metabolism
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Carcinoma / pathology
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Cell Line, Tumor
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Cell Movement / drug effects*
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Cell Movement / physiology*
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Cofilin 1 / drug effects
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Cofilin 1 / metabolism
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / pharmacology
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Fibronectins / metabolism
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Focal Adhesion Kinase 1 / drug effects
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Focal Adhesion Kinase 1 / metabolism
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Humans
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Integrins / drug effects
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Integrins / metabolism*
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Molecular Mimicry
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Paxillin / drug effects
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Paxillin / metabolism
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Phosphorylation
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Protein Kinase C-delta / antagonists & inhibitors
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Protein Kinase C-delta / metabolism
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Protein-Tyrosine Kinases / drug effects
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Protein-Tyrosine Kinases / metabolism
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Stomach Neoplasms / metabolism
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Stomach Neoplasms / pathology
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Tetradecanoylphorbol Acetate / pharmacology*
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Transforming Growth Factor beta / metabolism
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Transforming Growth Factor beta / pharmacology
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Transforming Growth Factor beta1
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rhoA GTP-Binding Protein / drug effects
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rhoA GTP-Binding Protein / metabolism
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src-Family Kinases
Substances
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Cofilin 1
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Enzyme Inhibitors
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Fibronectins
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Integrins
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Paxillin
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TGFB1 protein, human
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Transforming Growth Factor beta
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Transforming Growth Factor beta1
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Protein-Tyrosine Kinases
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CSK Tyrosine-Protein Kinase
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Focal Adhesion Kinase 1
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src-Family Kinases
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CSK protein, human
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Protein Kinase C-delta
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rhoA GTP-Binding Protein
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Tetradecanoylphorbol Acetate