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. |