The signaling network of transforming growth factor β1, protein kinase C delta, and integrin underlies the spreading and invasiveness of gastric carcinoma cells : The signaling network of transforming growth factor beta 1, protein kinase C delta, and integrin underlies the spreading and invasiveness of gastric carcinoma cells

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Lee, Mi-Sook; Kim, Tae Young; Kim, Yong-Bae; Lee, Sung-Yul; Ko, Seong-Gyu; Jong, Hyun-Soon; Kim, Tae-You; Bang, Yung-Jue; Lee, Jung Weon

Issue Date
American Society for Microbiology
Molecular and Cellular Biology, Vol.25 No.16, pp.6921-6936
Integrin-mediated cell adhesion and spreading enables cells to respond to extracellular stimuli for cellular functions. Using a gastric carcinoma cell line that is usually round in adhesion, we explored the mechanisms underlying the cell spreading process, separate from adhesion, and the biological consequences of the process. The cells exhibited spreading behavior through the collaboration of integrin-extracellular matrix interaction with a Smad-mediated transforming growth factor PI (TGF beta 1) pathway that is mediated by protein kinase C delta (PKC delta). TGF beta 1 treatment of the cells replated on extracellular matrix caused the expression and phosphorylation of PKC delta, which is required for expression and activation of integrins. Increased expression of integrins alpha 2 and alpha 3 correlated with the spreading, functioning in activation of focal adhesion molecules. Smad3, but not Smad2, overexpression enhanced the TGF beta 1 effects. Furthermore, TGF beta 1 treatment and PKC delta activity were required for increased motility on fibronectin and invasion through matrigel, indicating their correlation with the spreading behavior. Altogether, this study clearly evidenced that the signaling network, involving the Smad-dependent TGF beta pathway, PKC delta expression and phosphorylation, and integrin expression and activation, regulates cell spreading, motility, and invasion of the SNU16mAd gastric carcinoma cell variant.
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Graduate School of Convergence Science and Technology (융합과학기술대학원)Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과)Journal Papers (저널논문_분자의학 및 바이오제약학과)
College of Medicine/School of Medicine (의과대학/대학원)Dept. of Medicine (의학과)Journal Papers (저널논문_의학과)
College of Pharmacy (약학대학)Dept. of Pharmacy (약학과)Journal Papers (저널논문_약학과)
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