Oncotarget

Research Papers:

GATA2 as a potential metastasis-driving gene in prostate cancer

Yan Ting Chiang, Kendric Wang, Ladan Fazli, Robert Z. Qi, Martin E. Gleave, Colin C. Collins, Peter W. Gout and Yuzhuo Wang _

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Oncotarget. 2014; 5:451-461. https://doi.org/10.18632/oncotarget.1296

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Abstract

Yan Ting Chiang1,2, Kendric Wang2, Ladan Fazli2, Robert Z. Qi3, Martin E. Gleave2, Colin C. Collins2, Peter W. Gout1, Yuzhuo Wang1,2

1 Department of Experimental Therapeutics, BC Cancer Research Centre, Vancouver BC, Canada

2 The Vancouver Prostate Centre, Vancouver General Hospital and Department of Urologic Sciences, the University of British Columbia, Vancouver BC, Canada

3 Division of Life Science, the Hong Kong University of Science and Technology, Hong Kong

Correspondence:

Yuzhuo Wang, email:

Keywords: GATA2 gene, prostate cancer, metastasis, focal adhesion, master regulatory gene

Received: November 20, 2013 Accepted: January 12, 2014 Published: January 12, 2014

Abstract

Effective treatment for metastatic prostate cancer is critically needed. The present study was aimed at identifying metastasis-driving genes as potential targets for therapy (oncotargets). A differential gene expression profile of metastatic LTL-313H and non-metastatic LTL-313B prostate cancer tissue xenografts, derived from one patient’s specimen, was subjected to integrative analysis using the Ingenuity Upstream Regulator Analysis tool. Six candidate master regulatory genes were identified, including GATA2, a gene encoding a pioneer factor, a special transcription factor facilitating the recruitment of additional transcription factors. Elevated GATA2 expression in metastatic prostate cancer tissues correlated with poor patient prognosis. Furthermore, GATA2 gene silencing in human prostate cancer LNCaP cells led to a marked reduction in cell migration, tissue invasion, focal adhesion disassembly and to a dramatic change in cell transcriptomes, indicating that GATA2 plays a critical role in prostate cancer metastasis. As such, GATA2 could represent a prostate cancer metastasis-driving gene and a potential target for therapy of metastatic prostate cancer.


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