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

Shree Bose; Qiang Huang; Yunhan Ma; Lihua Wang; Grecia O Rivera; Yunxin Ouyang; Regina Whitaker; Rebecca A Gibson; Christopher D Kontos; Andrew Berchuck; Rebecca A Previs; Xiling Shen

doi:10.1016/j.celrep.2022.111012

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

Cell Rep. 2022 Jun 28;39(13):111012. doi: 10.1016/j.celrep.2022.111012.

Authors

Affiliations

¹ Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC 27708, USA; Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27708, USA.
² Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC 27708, USA; Department of Pediatric Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710006, China.
³ Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC 27708, USA.
⁴ Division of Gynecological Oncology, Duke Cancer Institute, Duke University Medical Center, Durham, NC 27708, USA.
⁵ Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27708, USA; Department of Medicine, Division of Cardiology, Duke University Medical Center, Durham, NC 27708, USA.
⁶ Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC 27708, USA; Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90024, USA. Electronic address: xiling.shen@terasaki.org.

Abstract

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.

Keywords: CP: Cancer; CP: Metabolism; metabolism; metastasis; ovarian cancer.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Carcinoma, Ovarian Epithelial
Female
Glucosephosphate Dehydrogenase* / metabolism
Humans
Omentum / metabolism
Ovarian Neoplasms*
Oxidative Stress
Pentose Phosphate Pathway
Tumor Microenvironment

Substances

Glucosephosphate Dehydrogenase

Abstract

Publication types

MeSH terms

Substances

Grants and funding