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Publication : c-Jun is required for TGF-β-mediated cellular migration via nuclear Ca²⁺ signaling.

First Author  Janowski E Year  2011
Journal  Int J Biochem Cell Biol Volume  43
Issue  8 Pages  1104-13
PubMed ID  21447400 Mgi Jnum  J:234609
Mgi Id  MGI:5790317 Doi  10.1016/j.biocel.2011.03.011
Citation  Janowski E, et al. (2011) c-Jun is required for TGF-beta-mediated cellular migration via nuclear Ca(2)(+) signaling. Int J Biochem Cell Biol 43(8):1104-13
abstractText  Tumor progression involves the acquisition of invasiveness through a basement membrane. The c-jun proto-oncogene is overexpressed in human tumors and has been identified at the leading edge of human breast tumors. TGF-beta plays a bifunctional role in tumorigenesis and cellular migration. Although c-Jun and the activator protein 1 (AP-1) complex have been implicated in human cancer, the molecular mechanisms governing cellular migration via c-Jun and the role of c-Jun in TGF-beta signaling remains poorly understood. Here, we analyze TGF-beta mediated cellular migration in mouse embryo fibroblasts using floxed c-jun transgenic mice. We compared the c-jun wild type with the c-jun knockout cells through the use of Cre recombinase. Herein, TGF-beta stimulated cellular migration and intracellular calcium release requiring endogenous c-Jun. TGF-beta mediated Ca(2+) release was independent of extracellular calcium and was suppressed by both U73122 and neomycin, pharmacological inhibitors of the breakdown of PIP(2) into IP(3). Unlike TGF-beta-mediated Ca(2+) release, which was c-Jun dependent, ATP mediated Ca(2+) release was c-Jun independent. These studies identify a novel pathway by which TGF-beta regulates cellular migration and Ca(2+) release via endogenous c-Jun.
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