Effect of cancer-associated mutations in the PlexinB1 gene

Molecular Cancer

Research

John R Masters¹  Magali Williamson¹  Oscar Gee-Wan Wong²  Chun Zhou³ 

[1] Prostate Cancer Research Centre, University College London, 67, Riding House Street, W1W 7EJ, London, UK;Prostate Cancer Research Centre, University College London, 67, Riding House Street, W1W 7EJ, London, UK;Department of Pathology, The University of Hong Kong, HKSAR, China;Prostate Cancer Research Centre, University College London, 67, Riding House Street, W1W 7EJ, London, UK;The Wistar Institute, 3601 Spruce Street, 19104, Philadelphia, PA, USA;

关键词: Plexin;    Prostate cancer;    Semaphorin;    Rac;    RhoD;    ErbB2;    c-Met;   

DOI  :  10.1186/1476-4598-11-11

 received in 2011-10-26, accepted in 2012-03-09,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundSemaphorins act as chemotactic cues for cell movement via their transmembrane receptors, plexins. Somatic missense mutations in the plexinB1 gene coupled with overexpression of the protein frequently occur in prostate tumours, indicating a role for plexinB1 in the pathogenesis of prostate cancer.ResultsTwo specific mutations found in prostate cancer enhance RhoD binding and one other mutation results in loss of inhibition of Rac-dependent Pak1 phosphorylation and lamellipodia formation and in impairment of trafficking of plexinB1 to the membrane. None of the three characterised mutations affect PDZRhoGEF binding, RhoA activity, the interaction of plexinB1with the oncogenes ErbB2 or c-Met or ErbB2 phosphorylation. The mutations have the net effect of increasing cell motility by blocking plexinB1-mediated inhibition of Rac while enhancing the interaction with RhoD, an anti-migratory factor.ConclusionsPlexinB1 mutations block plexinB1-mediated signalling pathways that inhibit cell motility.

【 授权许可】

Unknown   
© Zhou et al; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.