The role of GATA2 in lethal prostate cancer aggressiveness

Abstract

Advanced prostate cancer is a classic example of the intractability and consequent lethality that characterizes metastatic carcinomas. Novel treatments have improved the survival of men with prostate cancer; however, advanced prostate cancer invariably becomes resistant to these therapies and ultimately progresses to a lethal metastatic stage. Consequently, detailed knowledge of the molecular mechanisms that control prostate cancer cell survival and progression towards this lethal stage of disease will benefit the development of new therapeutics. The transcription factor endothelial transcription factor GATA-2 (GATA2) has been reported to have a key role in driving prostate cancer aggressiveness. In addition to being a pioneer transcription factor that increases androgen receptor (AR) binding and activity, GATA2 regulates a core subset of clinically relevant genes in an AR-independent manner. Functionally, GATA2 overexpression in prostate cancer increases cellular motility and invasiveness, proliferation, tumorigenicity, and resistance to standard therapies. Thus, GATA2 has a multifaceted function in prostate cancer aggressiveness and is a highly attractive target in the development of novel treatments against lethal prostate cancer.

Novel roles for GATAe in growth, maintenance and proliferation of cell populations in the Drosophila renal tubule

“…Our data indicate that knockdown of GATAe in PCs results in abnormal expression of different cancer and apoptosis-related genes in the adult Drosophila MTs. Our findings are in line with data from human GATA factors, which showed that GATA factors can act both as tumor suppressors or as oncogenes (Rodriguez-Bravo et al, 2017;Hellebrekers et al, 2009;Zheng and Blobel, 2010;Peters et al, 2014b).…”

Distinct Expression and Prognostic Values of GATA Transcription Factor Family in Human Ovarian Cancer.

“…Upregulated GATA2 expression has been implicated in several tumour types, such as breast cancer [41], colorectal cancer [42] and liver cancer [43]. Moreover, recent studies con rmed that GATA2 overexpression in prostate cancer increases cellular motility and invasiveness, proliferation, tumorigenicity, and resistance to standard therapies [40]. In our study, high expression of GATA2 was signi cantly associated with better OS, especially in pathological grade + OC patients.…”

“…GATA2 is identi ed as a critical regulator of growth, differentiation and survival of hematopoietic stem cells [39,40]. Increasing evidence has shown that GATA2 expression is correlated with hematologic pathophysiologies and the proliferation and progression of solid tumors [40]. Upregulated GATA2 expression has been implicated in several tumour types, such as breast cancer [41], colorectal cancer [42] and liver cancer [43].…”

Chromatin reprogramming as an adaptation mechanism in advanced prostate cancer

“…3) , Andreu-Vieyra et al 2011. GATA2 is an important mediator of androgen signaling within the hierarchical binding of other transcriptional regulators responsible for AR activity (Wang et al 2007, Jia et al 2008, Rodriguez-Bravo et al 2017) and has been shown to act downstream of FOXA1 in modulating AR binding to chromatin . FOXA1 has been further characterized as a pioneer factor for characterizing the AR and estrogen receptor (ER) cistromes in both prostate and breast cancer (Lupien et al 2008, Robinson et al 2011, Sahu et al 2011.…”