Title

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

Authors

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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