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Proc Natl Acad Sci U S A. 2018 May 8;115(19):4975-4980. doi: 10.1073/pnas.1721957115. Epub 2018 Apr 23.

COBLL1 modulates cell morphology and facilitates androgen receptor genomic binding in advanced prostate cancer.

Author information

1
Department of Functional Biogerontology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, 173-0015 Tokyo, Japan.
2
Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, 980-8575 Miyagi, Japan.
3
Department of Urology, The University of Tokyo, Bunkyo-ku, 113-8655 Tokyo, Japan.
4
Department of Urology, Nihon University School of Medicine, Itabashi-ku, 173-0032 Tokyo, Japan.
5
Department of Functional Biogerontology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, 173-0015 Tokyo, Japan; sinoue@tmig.or.jp.
6
Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Hidaka, 350-1241 Saitama, Japan.

Abstract

Androgen receptor (AR) signaling is essential for prostate cancer progression and acquiring resistance to hormone therapy. However, the molecular pathogenesis through AR activation has not been fully understood. We performed integrative transcriptomic analysis to compare the AR program in a castration-resistant prostate cancer (CRPC) model with that in their parental hormone-sensitive cells. We found that the gene cordon-bleu-like 1 (COBLL1) is highly induced by AR in CRPC model cells. The expression of COBLL1 that possesses an actin-binding domain is up-regulated in clinical prostate cancer tissues and is associated with a poor prognosis for prostate cancer patients. COBLL1 is involved in the cancer cell morphogenesis to a neuron-like cell shape observed in the CRPC model cells, promoting cell growth and migration. Moreover, nuclear COBLL1 interacts with AR to enhance complex formation with CDK1 and facilitates AR phosphorylation for genomic binding in CRPC model cells. Thus, our findings showed the mechanistic relevance of cordon-bleu proteins during the AR-mediated progression to CRPC.

KEYWORDS:

CDK1; COBLL1; androgen receptor; cell morphology; prostate cancer

PMID:
29686105
PMCID:
PMC5948986
DOI:
10.1073/pnas.1721957115
[Indexed for MEDLINE]
Free PMC Article

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