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|標題:||Elevated expression of protein kinase C delta induces cell scattering upon serum deprivation||作者:||Chen, C.L.
|關鍵字:||PKC delta;ROS;Cell scattering;Serum deprivation;focal-adhesion kinase;prostate-cancer cells;pkc-delta;induced;apoptosis;oxidative stress;proteolytic activation;tyrosine kinase;nadph oxidase;smooth-muscle;distinct mechanisms||Project:||Journal of Cell Science||期刊/報告no：:||Journal of Cell Science, Volume 123, Issue 17, Page(s) 2901-2913.||摘要:||
Tumor metastasis might be evoked in response to microenvironmental stress, such as a shortage of oxygen. Although the cellular response to hypoxia has been well established, we know little about how tumors adapt themselves to deprivation of growth factor. Protein kinase C delta (PKC delta), a stress-sensitive protein kinase, has been implicated in tumor progression. In this study, we demonstrate that elevated expression of PKC delta in Madin-Darby canine kidney cells induces a scatter response upon serum starvation, a condition that mimics growth-factor deprivation. Serum starvation stimulates the catalytic activity and Y311 phosphorylation of PKC delta through reactive oxygen species (ROS) and the Src family kinases. Mutation of PKC delta at Y311 and Y322, both of which are phosphorylation sites for Src, impairs its activation and ability to promote cell scattering upon serum deprivation. Once activated by ROS, PKC delta itself activates ROS production at least partially through NADPH oxidase. In addition, the c-Jun N-terminal kinase is identified as a crucial downstream mediator of ROS and PKC delta for induction of cell scattering upon serum deprivation. We demonstrate that the C1B domain of PKC delta is essential not only for its localization at the Golgi complex, but also for its activation and ability to induce cell scattering upon serum deprivation. Finally, depletion of PKC delta in human bladder carcinoma T24 cells restores their cell-cell contacts, which thereby reverses a scattered growth pattern to an epithelial-like growth pattern. Collectively, our results suggest that elevated expression of PKC delta might facilitate the scattering of cells in order to escape stress induced by growth-factor deprivation.
|Appears in Collections:||生命科學院|
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