Roles of proteolitic regulators in prostate cancer cell invasion.

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K16809
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Urology
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Ueda Saya (伊藤紗弥) 京都府立医科大学, 医学(系)研究科(研究院), 研究員 (90534511)
• Research Collaborator: UKIMURA Osamu
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: 前立腺癌 / タンパク分解制御 / 癌細胞浸潤

Outline of Final Research Achievements

To uncover the mechanism by which human prostate cancer progresses, we have previously performed a genetic screen for regulators of human prostate cancer progression using the Drosophila accessory gland. We found that CNPY2 and MEP1A markedly promoted cell growth and cell invasion of prostate cancer (PC) cells.
In this study, we suggested that CNPY2 controls AR protein levels in PC cells. Signaling by the androgen-induced AR has been known to be promote cell growth of PC cells. Our results suggested that CNPY2 promoted cell growth of PC cells by inhibition of AR protein degradation through MYLIP-mediated AR ubiquitination. In addition, we showed that CNPY2 interacted with several heat shock proteins. This result suggests that CNPY2 may control protein folding in cancer cells.
MEP1A, a metalloprotease is reported to be activated after propeptide cleaverage. In this study, we showed that active-type of MEP1A may be increased by androgen signal in PC cells.

Free Research Field

泌尿器科学

Academic Significance and Societal Importance of the Research Achievements

前立腺癌治療における課題は、ホルモン抵抗性癌に対する効果的治療法の開発である。ARの異常発現はホルモン抵抗性癌の細胞増殖の一因であると推測されており、ARのタンパク量制御メカニズムを明らかにした本研究成果は前立腺癌の進展メカニズムを理解する上での重要な知見と位置づけられ、今後の臨床分野への応用が期待される。
今後、CNPY2を介したタンパク質の量的・質的管理システム、およびホルモン抵抗性癌におけるMEP1A活性メカニズムに関して新たな知見を得ることで、ホルモン抵抗性前立腺癌に対する治療法の開発に繋がる分子メカニズムを明らかにできると考えられる