Integrin signaling and cell spreading mediated by phorbol 12-myristate 13-acetate treatment.
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.
Lee
Mi-Sook
MS
Department of Molecular and Clinical Oncology, Cancer Research Institute, College of Medicine, Seoul National University, 28 Yeongeon-dong, Jongno-gu, Seoul 110-799, Korea.
Kim
Yong-Bae
YB
Lee
Sung-Yul
SY
Kim
Jeong-Geun
JG
Kim
Sung-Hoon
SH
Ye
Sang-Kyu
SK
Lee
Jung Weon
JW
D000081247:CSK Tyrosine-Protein Kinase; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology*; D051338:Cofilin 1 / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005353:Fibronectins / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000187:drug effects / Q000378:metabolism*; D018716:Molecular Mimicry; D051419:Paxillin / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000187:drug effects / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology; D053773:Transforming Growth Factor beta1; D020742:rhoA GTP-Binding Protein / Q000187:drug effects / Q000378:metabolism; D019061:src-Family Kinases
D051338:Cofilin 1; D004791:Enzyme Inhibitors; D005353:Fibronectins; D016023:Integrins; D051419:Paxillin; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D051417:Focal Adhesion Kinase 1; D019061:src-Family Kinases; C000631346:CSK protein, human; D051745:Protein Kinase C-delta; D020742:rhoA GTP-Binding Protein; D013755:Tetradecanoylphorbol Acetate