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Publication : G6PD inhibition sensitizes ovarian cancer cells to oxidative stress in the metastatic omental microenvironment.

First Author  Bose S Year  2022
Journal  Cell Rep Volume  39
Issue  13 Pages  111012
PubMed ID  35767962 Mgi Jnum  J:357760
Mgi Id  MGI:7311478 Doi  10.1016/j.celrep.2022.111012
Citation  Bose S, et al. (2022) G6PD inhibition sensitizes ovarian cancer cells to oxidative stress in the metastatic omental microenvironment. Cell Rep 39(13):111012
abstractText  Ovarian cancer (OC) is the most lethal gynecological malignancy, with aggressive metastatic disease responsible for the majority of OC-related deaths. In particular, OC tumors preferentially metastasize to and proliferate rapidly in the omentum. Here, we show that metastatic OC cells experience increased oxidative stress in the omental microenvironment. Metabolic reprogramming, including upregulation of the pentose phosphate pathway (PPP), a key cellular redox homeostasis mechanism, allows OC cells to compensate for this challenge. Inhibition of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the PPP, reduces tumor burden in pre-clinical models of OC, suggesting that this adaptive metabolic dependency is important for OC omental metastasis.
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