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CACUL1 Functions as a Negative Regulator of Androgen Receptor in Prostate Cancer Cells

CACUL1 Functions as a Negative Regulator of Androgen Receptor in Prostate Cancer Cells

Hanbyeul Choi, Sang Hyup Lee, Soo-Jong Um, Eun-Joo Kim

Cancer Lett. 2016 Jul 1;376(2):360-6.

PMID: 27085459

Abstract:

The androgen receptor (AR) plays a critical role in the initiation and progression of prostate cancer (PCa), and thus its regulation is an important tool in PCa therapy. Here, we report that CDK2-associated cullin 1 (CACUL1) directly associates with AR and suppresses AR transcriptional activity. In addition, CACUL1 represses histone demethylase LSD1-mediated AR transactivation by competing with LSD1 for AR binding. Depletion of CACUL1 enhances the LSD1 occupancy of the AR-target promoter, accompanied by decreased accumulation of H3K9me2, a repressive transcriptional marker. CACUL1 and LSD1 oppositely regulate CDX-induced cell death in AR-positive LNCaP and metastatic castrate-resistant LNCaP-LN3 cells. These data suggest that CACUL1 impairs LSD1-mediated activation of AR, thereby implicating it as a potential antitumor target in PCa.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP90357065-A	Bicalutamide (CDX)		90357-06-5	Price

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