Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/127198
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
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 1476-5594 |
Statement of Responsibility: | 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 |
DOI: | 10.1038/s41388-020-1381-6 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/GNT1103006 |
Published version: | http://dx.doi.org/10.1038/s41388-020-1381-6 |
Appears in Collections: | Aurora harvest 8 Medicine publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.