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.
Highlights
Prostate cancer is the most commonly diagnosed non-cutaneous cancer and the second leading cause of cancer death for North American men [1]
In vitro evidence that GATA2 plays a role in prostate cancer metastasis, and the finding that its elevated expression in clinical metastatic prostate cancer tissues correlates with poor patient prognosis, suggest that the GATA2 gene is a potential prostate cancer metastasisdriving gene
Metastatic prostate cancer is highly resistant to conventional therapy and is at present incurable [5, 6]
Summary
Prostate cancer is the most commonly diagnosed non-cutaneous cancer and the second leading cause of cancer death for North American men [1]. Metastasis is generally thought to result from changes in the expression of specific, master regulatory genes that lead to cascades of downstream genes mediating the metastatic process. Such metastasis-driving genes could serve as therapeutic targets for management of metastatic prostate cancer [12,13,14]. The GATA2 gene is one of the six members of www.impactjournals.com/oncotarget the GATA transcription factor gene family that regulates cellular differentiation [22] It is known as the master regulator in the development of the hematopoietic system [23, 24]. Metastasis-driving genes may be identified by integrative analysis of gene expressions of metastatic and non-metastatic cancer cells. In vitro evidence that GATA2 plays a role in prostate cancer metastasis, and the finding that its elevated expression in clinical metastatic prostate cancer tissues correlates with poor patient prognosis, suggest that the GATA2 gene is a potential prostate cancer metastasisdriving gene
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