Redox signaling by glutathione peroxidase 2 links vascular modulation to metabolic plasticity of breast cancer

Ren, Zuen; Liang, Huizhi; Galbo, Phillip M.; Dharmaratne, Malindrie; Kulkarni, Ameya S.; Fard, Atefeh Taherian; Aoun, Marie Louise; Martinez-Lopez, Nuria; Suyama, Kimita; Benard, Outhiriaradjou; Zheng, Wei; Liu, Yang; Albanese, Joseph; Zheng, Deyou; Mar, Jessica C.; Singh, Rajat; Prystowsky, Michael B.; Norton, Larry; Hazan, Rachel B.

doi:10.1073/pnas.2107266119

Title: Redox signaling by glutathione peroxidase 2 links vascular modulation to metabolic plasticity of breast cancer

Journal Article · 22 February 2022 · Proceedings of the National Academy of Sciences of the United States of America

DOI: https://doi.org/10.1073/pnas.2107266119 · OSTI ID:2419585

^[1]; Liang, Huizhi ^[2]; Galbo, Phillip M. ^[2];

^[3];

^[2];

^[3];

^[2]; Martinez-Lopez, Nuria ^[2]; Suyama, Kimita ^[2]; Benard, Outhiriaradjou ^[2]; Zheng, Wei ^[4]; Liu, Yang ^[2]; Albanese, Joseph ^[2];

^[2]; Mar, Jessica C. ^[3];

^[2];

^[5];

^[2]

Albert Einstein College of Medicine, Bronx, NY (United States); OSTI
Albert Einstein College of Medicine, Bronx, NY (United States)
Univ. of Queensland, Brisbane, QLD (Australia)
Icahn School of Medicine at Mount Sinai, New York, NY (United States)
Memorial Sloan Kettering Cancer Center, New York, NY (United States)

Redox regulation of breast cancer underlies malignant progression. Loss of the antioxidant glutathione peroxidase 2 in breast cancer cells increases reactive oxygen species, thereby activating hypoxia inducible factor-α (HIF1α) signaling. This in turn causes vascular malfunction, resulting in hypoxia and metabolic heterogeneity. HIF1α suppresses oxidative phosphorylation and stimulates glycolysis (the Warburg effect) in most of the tumor, except for one cancer subpopulation, which was capable of using both metabolic modalities. Hence, adopting a hybrid metabolic state may allow tumor cells to survive under aerobic or hypoxic conditions, a vulnerability that may be exploited for therapeutic targeting by either metabolic or redox-based strategies.

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Research Organization:: Washington Univ., St. Louis, MO (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: SC0001035

OSTI ID:: 2419585

Journal Information:: Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 8 Vol. 119; ISSN 0027-8424

Publisher:: National Academy of SciencesCopyright Statement

Country of Publication:: United States

Language:: English

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Title: Redox signaling by glutathione peroxidase 2 links vascular modulation to metabolic plasticity of breast cancer

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