Journal article
Metabolic profiling of prostate cancer in skeletal microenvironments identifies G6PD as a key mediator of growth and survival
- Abstract:
- The spread of cancer to bone is invariably fatal, with complex cross-talk between tumor cells and the bone microenvironment responsible for driving disease progression. By combining in silico analysis of patient datasets with metabolomic profiling of prostate cancer cells cultured with bone cells, we demonstrate the changing energy requirements of prostate cancer cells in the bone microenvironment, identifying the pentose phosphate pathway (PPP) as elevated in prostate cancer bone metastasis, with increased expression of the PPP rate-limiting enzyme glucose-6-phosphate dehydrogenase (G6PD) associated with a reduction in progression-free survival. Genetic and pharmacologic manipulation demonstrates that G6PD inhibition reduces prostate cancer growth and migration, associated with changes in cellular redox state and increased chemosensitivity. Genetic blockade of G6PD in vivo results in reduction of tumor growth within bone. In summary, we demonstrate the metabolic plasticity of prostate cancer cells in the bone microenvironment, identifying the PPP and G6PD as metabolic targets for the treatment of prostate cancer bone metastasis.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 4.4MB, Terms of use)
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- Publisher copy:
- 10.1126/sciadv.abf9096
Authors
- Publisher:
- American Association for the Advancement of Science
- Journal:
- Science Advances More from this journal
- Volume:
- 8
- Issue:
- 8
- Article number:
- eabf9096
- Publication date:
- 2022-02-25
- Acceptance date:
- 2022-01-11
- DOI:
- EISSN:
-
2375-2548
- Pmid:
-
35213227
- Language:
-
English
- Keywords:
- Pubs id:
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1241408
- Local pid:
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pubs:1241408
- Deposit date:
-
2022-03-01
- ARK identifier:
Terms of use
- Copyright holder:
- Whitburn et al.
- Copyright date:
- 2022
- Rights statement:
- ©2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
- Licence:
- CC Attribution (CC BY)
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