期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2018
卷号：115
期号：19
页码：4975-4980
DOI：10.1073/pnas.1721957115
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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.
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