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

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.

Keywords: breast cancer; demethylase; hydroxylase; hypoxia; therapeutic strategy; αKG-dependent dioxygenases.