Metabolic profiling of prostate cancer in skeletal microenvironments identifies G6PD as a key mediator of growth and survival

Jessica Whitburn, Srinivasa R. Rao, Emma V. Morris, Sho Tabata, Akiyoshi Hirayama, Tomoyoshi Soga, James R. Edwards, Zeynep Kaya, Charlotte Palmer, Freddie C. Hamdy, Claire M. Edwards

研究成果: Article査読

抄録

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.

本文言語English
論文番号eabf9096
ジャーナルScience Advances
8
8
DOI
出版ステータスPublished - 2022 2月

ASJC Scopus subject areas

  • 一般

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