Cancer Cell：神经-成纤维细胞回路驱动结直肠癌进展

TL;DR - A Cancer Cell study identifies a self-amplifying nerve–fibroblast circuit that drives colorectal cancer progression, highlighting CHRM3 and NTN1 as potential therapeutic targets.

• Cholinergic signaling induces CHRM3/Gq-dependent NTN1 secretion from cancer-associated fibroblasts, which then increases intratumoral cholinergic innervation.
• Acetylcholine activates CHRM3–YAP signaling, while fibroblast-derived NTN1 promotes tumor growth and EMT-like programs through UNC5B–PI3K/AKT.
• Blocking CHRM3 or NTN1 suppressed these pathways and improved survival in mouse models.
• High NTN1 expression in human colorectal tumors correlated with mesenchymal-like disease and poorer prognosis.