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PROSTATE CANCER

ONECUT2 many towards AR-independence

Nature Reviews Urology volume 16, page 65 (2019)Cite this article

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Androgen receptor (AR) dependence is a defining characteristic of many metastatic castration-resistant prostate cancers (mCRPCs), but some aggressive tumours are AR-independent and rely on alternative transcriptional pathways. A new study has identified one cut domain family member 2 (ONECUT2) as a transcription factor that negatively regulates AR networks and drives AR-independent transcriptional programmes in mCRPC.

Transcriptomic and bioinformatic analyses in mCRPC cell line models revealed that ONECUT2 repressed AR and AR target gene expression. Importantly, ONECUT2 transcriptional activity — inferred using a bioinformatics approach — inversely correlated with an AR transcriptomic signature in the discovery cohort, suggesting that ONECUT2 antagonizes AR and its transcriptional programme. Furthermore, multiplex immunofluorescence microscopy coupled to digital pathology in high-grade prostate cancer tissues revealed that nuclear ONECUT2 and AR expression were inversely correlated in ONECUT2+AR+ cells.

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References

Original article

  • Rotinen, M. et al. ONECUT2 is a targetable master regulator of lethal prostate cancer that suppresses the androgen axis. Nat. Med. 24, 1887–1898 (2018)

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  1. Nature Reviews Urology http://www.nature.com/nrurol/

    Conor A. Bradley

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  1. Conor A. Bradley
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Correspondence to Conor A. Bradley.

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Bradley, C.A. ONECUT2 many towards AR-independence. Nat Rev Urol 16, 65 (2019). https://doi.org/10.1038/s41585-018-0136-4

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