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The role of GATA2 in lethal prostate cancer aggressiveness

This article has been updated

Key Points

  • Endothelial transcription factor GATA-2 (GATA2) is a pioneer, master-regulator, transcription factor that binds DNA regions of closed chromatin, causing opening and facilitating subsequent hierarchical binding of other regulators that activate transcription

  • GATA2 is crucial for the development of the genitourinary system and might be a lineage marker of mouse and human prostate tissue

  • GATA2 drives androgen-responsive gene expression and contributes to prostate cancer metastasis by increasing tumour cell motility and invasiveness in early stages of the disease, through its pioneer transcription factor function

  • GATA2 is important in prostate cancer progression to an androgen-refractory state and regulates an androgen-independent signalling network in late stages of the disease

  • Preclinical experimental data have demonstrated the utility of inhibiting GATA2 through targeting its upstream regulators, post-translational modifications, and downstream effectors

  • Integrating GATA2 inhibition into the therapeutic landscape of prostate cancer will require the development of precise predictive assays and identification of the most effective therapeutic combination

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.

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Figure 1: The pioneer endothelial transcription factor GATA-2 (GATA2).
Figure 2: Endothelial transcription factor GATA-2 (GATA2) regulates lethal prostate cancer aggressiveness.
Figure 3: Different strategies for targeting endothelial transcription factor GATA-2 (GATA2) in prostate cancer.

Change history

  • 25 November 2016

    In the original version of this article the acknowledgements section was omitted. This has been corrected in the print and online versions of the manuscript.

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Acknowledgements

V.R.-B. receives funding from the U.S. Department of Health & Human Services, NIH, National Cancer Institute grant number 1 K22 CA207458-01 and J.D.-D. receives funding from U.S. Department of Health & Human Services, NIH, National Cancer Institute grant number 1 R01 CA207311-01.

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Rodriguez-Bravo, V., Carceles-Cordon, M., Hoshida, Y. et al. The role of GATA2 in lethal prostate cancer aggressiveness. Nat Rev Urol 14, 38–48 (2017). https://doi.org/10.1038/nrurol.2016.225

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