Choline Kinase Alpha as Androgen Receptor Chaperone and Prostate Cancer Target

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As reported in the Journal of the National Cancer Institute, Asim and colleagues found that choline kinase alpha (CHKA) acts as a chaperone for the androgen receptor (AR) and may serve as a therapeutic target in prostate cancer.

CHKA expression was found to be androgen regulated in cell lines, xenografts, and human tissue and was positively associated with tumor stage in a large number of benign, prostatic intraepithelial neoplasia, and prostate cancer lesions examined. CHKA was found to bind directly to the ligand-binding domain of the AR and to enhance AR stability—thus becoming the first kinase to be identified as an AR chaperone. Inhibition of CHKA reduced activity of the AR transcriptional program, including inhibition of pathways for regulation of protein folding; decreased AR protein levels; and inhibition of the growth of prostate cancer cell lines, human prostate cancer explants, and tumor xenografts.

The investigators concluded:

“CHKA can act as an AR chaperone, providing, to our knowledge, the first evidence for kinases as molecular chaperones, making CHKA both a marker of tumor progression and a potential therapeutic target for [prostate cancer].

Asim M, et al: J Natl Cancer Inst 108:djv371, 2015.




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