Summary
Published in Advanced Science (2026), this peer-reviewed study used 3D Petri Dish® micro-molds to form scaffold-free 3D microtissues. Full citation: Yang, Jianqiang, et al. GLS1 Orchestrates Exosome‐Mediated Tumor‐Endothelial Communication to Facilitate Angiogenesis
GLS1 Orchestrates Exosome‐Mediated Tumor‐Endothelial Communication to Facilitate Angiogenesis
Research Overview
Glutaminase 1 fuels tumor growth through glutaminolysis, but its influence on the surrounding microenvironment was unclear. This study shows that in head and neck squamous cell carcinoma, GLS1 promotes angiogenesis through an exosome-dependent route: silencing GLS1 or treating with the inhibitor CB-839 markedly reduced blood vessel formation inside xenograft tumors.
Exosomes from GLS1-deficient cells impaired endothelial migration and tube formation. Proteomics traced this to loss of the pro-angiogenic protein Tenascin C from those exosomes. Mechanistically, GLS1 loss disrupts USP1-mediated deubiquitination of Caveolin-1, so Caveolin-1 is degraded and can no longer recruit Tenascin C into exosomes — cutting the signal that would otherwise activate integrin–FAK signaling in endothelial cells.
Key Discoveries
- GLS1 silencing or CB-839 treatment markedly reduced intratumoral angiogenesis in HNSCC xenografts
- Exosomes from GLS1-deficient cells lacked Tenascin C and failed to drive endothelial migration and tube formation
- GLS1 sustains USP1-mediated deubiquitination of Caveolin-1, which is required to load Tenascin C into exosomes
