The R(h)oads to Stat3: Stat3 activation by the Rho GTPases

    Authors

    L. Raptis; R. Arulanandam; M. Geletu;J. Turkson

    Comments

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    Abbreviated Journal Title

    Exp. Cell Res.

    Keywords

    Rho GTPases; MgcRacGAP; Stat3; CELL-CELL ADHESION; FULL NEOPLASTIC TRANSFORMATION; SRC-INDUCED; TRANSFORMATION; EPITHELIAL DOME FORMATION; LARGE TUMOR-ANTIGEN; FAMILY; GTPASES; INTERCELLULAR-ADHESION; TRANSCRIPTION FACTORS; SIGNAL; TRANSDUCER; NHE3 EXPRESSION; Oncology; Cell Biology

    Abstract

    The signal transducer and activator of transcription-3 (Stat3) is a member of the STAT family of cytoplasmic transcription factors. Overactivation of Stat3 is detected with high frequency in human cancer and is considered a molecular abnormality that supports the tumor phenotype. Despite concerted investigative efforts, the molecular mechanisms leading to the aberrant Stat3 activation and Stat3-mediated transformation and tumorigenesis are still not clearly defined. Recent evidence reveals a crosstalk close relationship between Stat3 signaling and members of the Rho family of small GTPases, including Rac1, Cdc42 and RhoA. Specifically, Rac1, acting in a complex with the MgcRacGAP (male germ cell RacGAP), promotes tyrosine phosphorylation of Stat3 by the IL6-receptor family/jak kinase complex, as well as its translocation to the nucleus. Studies have further revealed that the mutational activation of Rac1 and Cdc42 results in Stat3 activation, which occurs in part through the upregulation of IL6 family cytokines that in turn stimulates Stat3 through the Jak kinases. Interestingly, evidence also shows that the engagement of cadherins, cell to cell adhesion molecules, specifically induces a striking increase in Rac1 and Cdc42 protein levels and activity, which in turn results in Stat3 activation. In this review we integrate recent findings clarifying the role of the Rho family GTPases in Stat3 activation in the context of malignant progression. (C) 2011 Elsevier Inc. All rights reserved.

    Journal Title

    Experimental Cell Research

    Volume

    317

    Issue/Number

    13

    Publication Date

    1-1-2011

    Document Type

    Review

    Language

    English

    First Page

    1787

    Last Page

    1795

    WOS Identifier

    WOS:000292409300001

    ISSN

    0014-4827

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