Open AccessRedox signaling by glutathione peroxidase 2 links vascular modulation to metabolic plasticity of breast cancer
Author(s) -
Zuen Ren,
Hongying Liang,
Phillip M. Galbo,
Malindrie Dharmaratne,
Ameya Kulkarni,
Atefeh Taherian Fard,
Marie Louise Aoun,
Nuria Martínez–López,
Kimita Suyama,
Outhiriaradjou Benard,
Wei Zheng,
Yang Liu,
Joseph Albanese,
Deyou Zheng,
Jessica C. Mar,
Rajat Singh,
Michael B. Prystowsky,
Larry Norton,
Rachel B. Hazan
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2107266119
Subject(s) - biology , angiogenesis , cancer research , warburg effect , glycolysis , microbiology and biotechnology , biochemistry , metabolism
Significance 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.