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Int J Biochem Cell Biol. 2011 Aug;43(8):1104-13. doi: 10.1016/j.biocel.2011.03.011. Epub 2011 Apr 5.

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

Author information

1
Department of Pharmacology, Georgetown University, 3900 Reservoir Road, NW, Washington, DC 20057, United States.

Abstract

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-β 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-β signaling remains poorly understood. Here, we analyze TGF-β 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-β stimulated cellular migration and intracellular calcium release requiring endogenous c-Jun. TGF-β 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-β-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-β regulates cellular migration and Ca(2+) release via endogenous c-Jun.

PMID:
21447400
DOI:
10.1016/j.biocel.2011.03.011
[Indexed for MEDLINE]

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