Tumour acidosis remodels the glycocalyx to control lipid scavenging and ferroptosis - PubMed
3 months ago
- #tumour acidosis
- #glycocalyx
- #ferroptosis
- Tumour acidosis remodels the glycocalyx to control lipid scavenging and ferroptosis.
- Aggressive tumours adapt to microenvironmental stress and metabolic reprogramming, with lipid droplet accumulation as a key strategy to buffer toxic lipids and suppress ferroptosis.
- A chondroitin sulfate (CS)-enriched glycocalyx is identified as a hallmark of the acidic microenvironment in glioblastoma and CNS metastases, protecting against lipid-induced ferroptosis.
- Hypoxia-inducible factor and transforming growth factor beta signalling induce a glycan switch on syndecan-1, replacing heparan sulfate with CS, impairing lipid-scavenging function.
- Dual inhibition of CS biosynthesis and diacylglycerol O-acyltransferase-1 triggers lipid peroxidation and ferroptotic cell death.
- The study highlights glycan remodelling as a core determinant of metabolic plasticity and positions the glycocalyx as a regulator of nutrient access and therapeutic vulnerability in cancer.