Pharmacologically targetable vulnerability in prostate cancer carrying RB1-SUCLA2 deletion

Susumu Kohno, Paing Linn, Naoko Nagatani, Yoshihiro Watanabe, Sharad Kumar, Tomoyoshi Soga, Chiaki Takahashi

研究成果: Article査読

1 被引用数 (Scopus)


RB1 gene is often homozygously deleted or mutated in prostate adenocarcinomas following acquirement of castration resistance and/or metastatic ability. We found that SUCLA2 gene is frequently involved in the deletion of the RB1 gene region in advanced prostate cancer. SUCLA2 constitutes the β-subunit of succinate CoA ligase heterodimer that reversibly converts succinyl CoA into succinate. We sought the possibility that deletion of SUCLA2 gives rise to a metabolic vulnerability that could be targeted therapeutically. We found a significant metabolic shift in SUCLA2-deleted prostate cancer cells, including lower mitochondrial respiratory activity. By screening a number of libraries for compounds that induce cell death selectively in SUCLA2-deficient prostate cancer cells, we identified thymoquinone (2-isopropyl-5-methylbenzo-1,4-quinone) and PMA (phorbol-12-myristate-13-acetate) from a natural compound library. These findings indicate that the metabolic vulnerability in SUCLA2-deficient prostate cancer cells is pharmacologically targetable.

出版ステータスPublished - 2020 8 20

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

フィンガープリント 「Pharmacologically targetable vulnerability in prostate cancer carrying RB1-SUCLA2 deletion」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。