Giovanni Fucà, Medical Director, Early Global Development, Oncology RandD at AstraZeneca, shared a post on LinkedIn:
“In the acidic niche, tumour cells build a biochemical armour that decides which nutrients get in (and which lethal signals stay out).
A new study in Nature Cell Biology shows that tumour acidosis induces a profound remodelling of the glycocalyx, creating a chondroitin sulphate-rich barrier that rewires how cancer cells access (and restrict) extracellular lipids.
Key insights:
- Acidosis triggers a glycan switch. Cooperative HIF and TGF‑β signalling upregulate CSGALNACT1, replacing HS with CS on proteoglycans.
- This CS‑enriched glycocalyx blocks lipid scavenging. It prevents the uptake of LDL, HDL and EV-derived lipids by disrupting the HS‑dependent function of **syndecan‑1 (SDC1).
- Tumour cells create a dual-layer metabolic defence:
A CS ‘shield’ restricting external lipid access
A lipid droplet ‘sink’ buffering toxic lipids internally
- Together, they allow survival under metabolic stress and protect from lipid peroxidation and ferroptosis.
Therapeutic implications:
- Blocking CS biosynthesis restores lipid uptake and exposes tumour cells to lipotoxicity.
- DGAT1 inhibition disrupts lipid droplet formation.
- Combining both approaches unleashes ferroptosis, driving catastrophic lipid peroxidation and improving survival in an orthotopic GBM model.
This work highlights how surface glycosylation becomes a master regulator of metabolic fitness and reveals a ferroptosis vulnerability uniquely exposed in acidic, lipid-stressed tumour niches.”
Title: Tumour acidosis remodels the glycocalyx to control lipid scavenging and ferroptosis
Authors: Anna Bång-Rudenstam, Myriam Cerezo-Magaña, Marton Horvath, Hugo Talbot, Emma Gustafsson, Stevanus Jonathan, Chaitali Chakraborty, Itzel Nissen, Kelin Gonçalves de Oliveira, Axel Boukredine, Sarah Beyer, Julio Enriquez Perez, Maria C. Johansson, Lena Kjellén, Emil Tykesson, Anders Malmström, Toin H. van Kuppevelt, Karin Forsberg-Nilsson, Jeffrey D. Esko, Silvia Remeseiro, Johan Bengzon, Valeria Governa, Mattias Belting
Read the Full Article.
More about Ferroptosis on OncaDaily.