α-Ketoglutarate-dependent Enzymes in Breast Cancer and Therapeutic Implications.

Jingjing Xiong, Chaojun Yan, Qing Zhang, Jing Zhang

Journal: Endocrinology 2023;164(6):bqad080

PMID: 37207449

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Abstract

α-Ketoglutarate (αKG)-dependent dioxygenases are a superfamily of enzymes that require oxygen, reduced iron, and αKG for their catalytic functions. Therefore, they have the potential to sense the availabilities of oxygen, iron, and specific metabolites, including αKG and its structurally related metabolites. These enzymes play essential roles in various biological processes, including cellular adaptation to hypoxia, epigenetic and epitranscriptomic regulation of gene expression, and metabolic reprogramming. Many αKG-dependent dioxygenases are dysregulated in cancer pathogenesis. Herein, we review how they are regulated and function in breast cancer, which may offer new therapeutic intervention strategies for targeting this family of enzymes.

Address: Department of Thyroid and Breast Surgery, Medical Research Institute, Frontier Science Center for Immunology and Metabolism, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China.; Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.; Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

DOI: 10.1210/endocr/bqad080

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MeSH Terms: Humans, Female, Breast Neoplasms, Ketoglutaric Acids, Iron, Dioxygenases, Oxygen