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The signaling network of transforming growth factor beta1, protein kinase Cdelta, and integrin underlies the spreading and invasiveness of gastric carcinoma cells

Cited 37 time in Web of Science Cited 38 time in Scopus
Authors

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

Issue Date
2005
Publisher
American Society for Microbiology
Citation
Mol. Cell. Biol. 25:6921-6936
Keywords
TGFadhesionspreadinggastric cancer
Abstract
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 beta1 (TGFbeta1) pathway that is mediated by protein kinase Cdelta (PKCdelta). TGFbeta1 treatment of the cells replated on extracellular matrix caused the expression and phosphorylation of PKCdelta, which is required for expression and activation of integrins. Increased expression of integrins alpha2 and alpha3 correlated with the spreading, functioning in activation of focal adhesion molecules. Smad3, but not Smad2, overexpression enhanced the TGFbeta1 effects. Furthermore, TGFbeta1 treatment and PKCdelta 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 TGFbeta pathway, PKCdelta expression and phosphorylation, and integrin expression and activation, regulates cell spreading, motility, and invasion of the SNU16mAd gastric carcinoma cell variant.
ISSN
0270-7306
Language
English
URI
http://mcb.asm.org

https://hdl.handle.net/10371/3232
DOI
https://doi.org/10.1128/MCB.25.16.6921-6936.2005
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