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|Title:||Pharmacologically targetable vulnerability in prostate cancer carrying RB1-SUCLA2 deletion|
|Citation:||Oncogene, 2020; 39(34):5690-5707|
|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|
|Appears in Collections:||Medicine publications|
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