GATA2 as a potential metastasis-driving gene in prostate cancer

被引:52
|
作者
Chiang, Yan Ting [1 ,2 ,3 ]
Wang, Kendric [2 ,3 ]
Fazli, Ladan [2 ,3 ]
Qi, Robert Z. [4 ]
Gleave, Martin E. [2 ,3 ]
Collins, Colin C. [2 ,3 ]
Gout, Peter W. [1 ]
Wang, Yuzhuo [1 ,2 ,3 ]
机构
[1] BC Canc Res Ctr, Dept Expt Therapeut, Vancouver, BC, Canada
[2] Univ British Columbia, Vancouver Gen Hosp, Vancouver Prostate Ctr, Vancouver, BC V5Z 1M9, Canada
[3] Univ British Columbia, Dept Urol Sci, Vancouver, BC V5Z 1M9, Canada
[4] Hong Kong Univ Sci & Technol, Div Life Sci, Hong Kong, Hong Kong, Peoples R China
基金
加拿大健康研究院;
关键词
GATA2; gene; prostate cancer; metastasis; focal adhesion; master regulatory gene; TRANSCRIPTION FACTORS; RADIATION-THERAPY; CELL-MIGRATION; EXPRESSION; NETWORK; PHENOTYPE; REGIONS; PROTEIN; LIGAND; MODEL;
D O I
10.18632/oncotarget.1296
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:451 / 461
页数:11
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