Literature DB >> 17018616

HER2/Neu (ErbB2) signaling to Rac1-Pak1 is temporally and spatially modulated by transforming growth factor beta.

Shizhen Emily Wang1, Incheol Shin, Frederick Y Wu, David B Friedman, Carlos L Arteaga.   

Abstract

In HER2 (ErbB2)-overexpressing cells, transforming growth factor beta (TGF-beta), via activation of phosphoinositide-3 kinase (PI3K), recruits actin and actinin to HER2, which then colocalizes with Vav2, activated Rac1, and Pak1 at cell protrusions. This results in prolonged Rac1 activation, enhanced motility and invasiveness, Bad phosphorylation, uncoupling of Bad/Bcl-2, and enhanced cell survival. The recruitment of the HER2/Vav2/Rac1/Pak1/actin/actinin complex to lamellipodia was abrogated by actinin siRNAs, dominant-negative (dn) p85, gefitinib, and dn-Rac1 or dn-Pak1, suggesting that the reciprocal interplay of PI3K, HER2 kinase, and Rac GTPases with the actin cytoskeleton is necessary for TGF-beta action in oncogene-overexpressing cells. Thus, by recruiting the actin skeleton, TGF-beta "cross-links" this signaling complex at cell lamellipodia; this prolongs Rac1 activation and increases metastatic properties and survival of HER2-overexpressing cells.

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Year:  2006        PMID： 17018616     DOI： 10.1158/0008-5472.CAN-06-2071

Source DB:  PubMed          Journal:  Cancer Res        ISSN： 0008-5472            Impact factor:   12.701


  60 in total

1.  Convergence of p53 and transforming growth factor beta (TGFbeta) signaling on activating expression of the tumor suppressor gene maspin in mammary epithelial cells.

Authors:  Shizhen Emily Wang; Archana Narasanna; Corbin W Whitell; Frederick Y Wu; David B Friedman; Carlos L Arteaga
Journal:  J Biol Chem       Date:  2007-01-04       Impact factor: 5.157

2.  A mathematical model quantifies proliferation and motility effects of TGF-β on cancer cells.

Authors:  Shizhen Emily Wang; Peter Hinow; Nicole Bryce; Alissa M Weaver; Lourdes Estrada; Carlos L Arteaga; Glenn F Webb
Journal:  Comput Math Methods Med       Date:  2009-03       Impact factor: 2.238

3.  Linear Chains of HER2 Receptors Found in the Plasma Membrane Using Liquid-Phase Electron Microscopy.

Authors:  Kelly Parker; Patrick Trampert; Verena Tinnemann; Diana Peckys; Tim Dahmen; Niels de Jonge
Journal:  Biophys J       Date:  2018-06-18       Impact factor: 4.033

4.  Nuclear translocation of type I transforming growth factor β receptor confers a novel function in RNA processing.

Authors:  Manasa Chandra; Shengbing Zang; Haiqing Li; Lisa J Zimmerman; Jackson Champer; Akihiro Tsuyada; Amy Chow; Weiying Zhou; Yang Yu; Harry Gao; Xiubao Ren; Ren-Jang Lin; Shizhen Emily Wang
Journal:  Mol Cell Biol       Date:  2012-04-02       Impact factor: 4.272

5.  HER2/ErbB2-induced breast cancer cell migration and invasion require p120 catenin activation of Rac1 and Cdc42.

Authors:  Emhonta Johnson; Darcie D Seachrist; Carlos M DeLeon-Rodriguez; Kristen L Lozada; John Miedler; Fadi W Abdul-Karim; Ruth A Keri
Journal:  J Biol Chem       Date:  2010-07-01       Impact factor: 5.157

6.  The SHCA adapter protein cooperates with lipoma-preferred partner in the regulation of adhesion dynamics and invadopodia formation.

Authors:  Alex Kiepas; Elena Voorand; Julien Senecal; Ryuhjin Ahn; Matthew G Annis; Kévin Jacquet; George Tali; Nicolas Bisson; Josie Ursini-Siegel; Peter M Siegel; Claire M Brown
Journal:  J Biol Chem       Date:  2020-04-16       Impact factor: 5.157

7.  Transforming growth factor beta induces clustering of HER2 and integrins by activating Src-focal adhesion kinase and receptor association to the cytoskeleton.

Authors:  Shizhen Emily Wang; Bin Xiang; Roy Zent; Vito Quaranta; Ambra Pozzi; Carlos L Arteaga
Journal:  Cancer Res       Date:  2009-01-15       Impact factor: 12.701

8.  Oncogenic mutations regulate tumor microenvironment through induction of growth factors and angiogenic mediators.

Authors:  S E Wang; Y Yu; T L Criswell; L M Debusk; P C Lin; R Zent; D H Johnson; X Ren; C L Arteaga
Journal:  Oncogene       Date:  2010-04-12       Impact factor: 9.867

9.  A Rac-Pak signaling pathway is essential for ErbB2-mediated transformation of human breast epithelial cancer cells.

Authors:  L E Arias-Romero; O Villamar-Cruz; A Pacheco; R Kosoff; M Huang; S K Muthuswamy; J Chernoff
Journal:  Oncogene       Date:  2010-08-16       Impact factor: 9.867

10.  Cucurbitacin I inhibits Rac1 activation in breast cancer cells by a reactive oxygen species-mediated mechanism and independently of Janus tyrosine kinase 2 and P-Rex1.

Authors:  Cynthia Lopez-Haber; Marcelo G Kazanietz
Journal:  Mol Pharmacol       Date:  2013-03-11       Impact factor: 4.436
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