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Type: Journal article
Title: Pharmacologically targetable vulnerability in prostate cancer carrying RB1-SUCLA2 deletion
Author: Kohno, S.
Linn, P.
Nagatani, N.
Watanabe, Y.
Kumar, S.
Soga, T.
Takahashi, C.
Citation: Oncogene, 2020; 39(34):5690-5707
Publisher: Springer Nature
Issue Date: 2020
ISSN: 1476-5594
Statement of
Susumu Kohno, Paing Linn, Naoko Nagatani, Yoshihiro Watanabe, Sharad Kumar, Tomoyoshi Soga, Chiaki Takahashi
Abstract: 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.
Keywords: Cell Line, Tumor; Animals; Mice, Knockout; Humans; Mice, Nude; Mice, SCID; Prostatic Neoplasms; Tetradecanoylphorbol Acetate; Benzoquinones; Succinate-CoA Ligases; Retinoblastoma Protein; Apoptosis; Gene Deletion; Male; HEK293 Cells; PC-3 Cells
Rights: © The Author(s), under exclusive licence to Springer Nature Limited 2020
RMID: 1000024018
DOI: 10.1038/s41388-020-1381-6
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Appears in Collections:Medicine publications

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