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

Einsley Janowski, Xuanmao Jiao, Sanjay Katiyar, Michael P. Lisanti, Manran Liu, Richard G. Pestell, Martin Morad

    Research output: Contribution to journalArticlepeer-review


    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 Ca2+ release was independent of extracellular calcium and was suppressed by both U73122 and neomycin, pharmacological inhibitors of the breakdown of PIP2 into IP 3. Unlike TGF-β-mediated Ca2+ release, which was c-Jun dependent, ATP mediated Ca2+ release was c-Jun independent. These studies identify a novel pathway by which TGF-β regulates cellular migration and Ca2+ release via endogenous c-Jun.
    Original languageEnglish
    Pages (from-to)1104-1113
    Number of pages9
    JournalInternational Journal of Biochemistry and Cell Biology
    Issue number8
    Publication statusPublished - Aug 2011


    • Calcium
    • Calcium imaging
    • Cell migration
    • Inositol phosphates
    • Tranforming growth factor beta


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