exploring innovative therapeutic target for bone metastatic prostate cancer based on analysis of molecular mechanism.

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K09168
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Ehime University
• Principal Investigator: SAIKA TAKASHI 愛媛大学, 医学系研究科, 教授 (10314676)
• Co-Investigator(Kenkyū-buntansha): 今井 祐記 愛媛大学, プロテオサイエンスセンター, 教授 (10423873) ; 菊川 忠彦 愛媛大学, 医学系研究科, 准教授 (70444734) ; 三浦 徳宣 愛媛大学, 医学部附属病院, 講師 (80554427)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 前立腺癌 / 骨転移

Outline of Final Research Achievements

The prognosis of patients with progressive prostate cancers that are hormone refractory and/or have bone metastasis is poor. we identified G Protein-Coupled Receptor Class C Group 5 Member A (GPRC5A) as a candidate therapeutic molecule using integrative gene expression analyses of registered data sets for prostate cancer cell lines. Kaplan Meier analysis of TCGA data sets revealed that patients who have high GPRC5A expression had significantly shorter overall survival. PC3 prostate cancer cells with CRISPR/Cas9-mediated GPRC5A knockout exhibited significantly reduced cell proliferation both in vitro and in vivo. RNA-seq revealed that GPRC5A KO PC3 cells had dysregulated expression of cell cycle-related genes, leading to cell cycle arrest at the G2/M phase. Furthermore, GPRC5A KO PC3 cells failed to establish bone metastasis in xenograft mice models. Our findings indicate that GPRC5A can be a possible therapeutic target and prognostic marker molecule for progressive prostate cancer.

Free Research Field

腎泌尿器科学

Academic Significance and Societal Importance of the Research Achievements

本研究の成果により、前立腺癌進展の病態の解明と新規治療方法および骨転移の予防や骨転移発生の予測の治療基盤の構築が進むと期待できる。