The Intersection of Glycosylation and Ferroptosis in Cancer.

Abstract

Ferroptosis, an iron-dependent form of regulated cell death characterized by lipid peroxidation, has emerged as a critical mechanism in cancer biology and therapy. Aberrant glycosylation is a hallmark of cancer, influencing cellular processes from proliferation to immune evasion. Recent evidence has revealed previously underappreciated crosstalk between glycosylation and ferroptosis in cancer cells, where specific glycosylation modifications can determine cellular susceptibility to ferroptotic cell death. This review summarizes the current understanding of how N-linked glycosylation, O-linked glycosylation, and glycosaminoglycan biosynthesis modulate sensitivity to ferroptosis in various cancers. We examine the molecular mechanisms underlying glycosylation-dependent ferroptosis regulation, including the roles of key glycosyltransferases and glycan structures in the oxidative stress response. Furthermore, we discuss the therapeutic potential of targeting the glycosylation-ferroptosis axis for cancer treatment in this emerging field.