Loss of Gαq reshapes fibroblast traits and drives tumor-stroma remodeling in oral cancer progression - PubMed
3 hours ago
- #Cancer-Associated Fibroblasts
- #Gαq Protein
- #Tumor Microenvironment
- Loss of Gαq reprograms fibroblasts into a cancer-associated fibroblast (CAF)-like phenotype through deregulated intracellular trafficking and increased ceramide accumulation.
- Gαq-deficient fibroblasts exhibit enhanced collagen I deposition, extracellular matrix (ECM) remodeling, and secretion, promoting tumor progression in head and neck squamous cell carcinoma (HNSCC).
- Exosomes from Gαq-silenced fibroblasts are enriched with tumor-promoting growth factor receptors, suppress Caveolin-1 in tumor cells, and induce an EMT-like phenotype that fuels HNSCC growth and invasion.
- In co-culture and in vivo, Gαq-deficient fibroblasts form 'railroad-track' structures that guide cancer cell migration and invasion, and reduced Gαq expression in human fibroblasts recapitulates these features.
- Gαq is identified as a key regulator of fibroblast plasticity and tumor-stroma interactions in HNSCC progression, with implications for understanding vesicle trafficking pathways in the tumor microenvironment.