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

Ken ichi Takayama, Takashi Suzuki, Tetsuya Fujimura, Satoru Takahashi, Satoshi Inoue

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4975-4980
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number19
DOIs
Publication statusPublished - 2018 May 8

Keywords

  • Androgen receptor
  • CDK1
  • COBLL1
  • Cell morphology
  • Prostate cancer

ASJC Scopus subject areas

  • General

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