Figure: reconstruction of a precancerous lesion (yellow) and its sympathetic innervation network (axons in green, branch points in pink), from 3D images acquired by light-sheet fluorescence microscopy.

The nervous system does more than transmit signals between the brain and the body: it actively interacts with tissues and influences their integrity. In the pancreas, sympathetic nerve fibers reorganize around early precancerous lesions, well before the onset of cancer. This study, conducted by Hiba Haidar and colleagues at IBDM in collaboration with Patrick Mehlen’s team, shows that this remodeling is orchestrated by Netrin-1, an axon guidance molecule produced by the cells of precancerous lesions. Netrin-1 promotes the growth and branching of nerve fibers, forming a network that modulates the proliferation of precancerous cells. When Netrin-1 is inhibited, nerve plasticity decreases and the lesions develop more rapidly. Thus, nerve plasticity serves as a protective mechanism during the early stages of pancreatic carcinogenesis. These findings could open new avenues for the early detection of precancerous lesions and for slowing their progression toward cancer.

Haidar H, Bellon A, Sleiman K, Hocine M, Rama N, Gadot N, Carpizo DR, Mehlen P, Mann F. Neural function of Netrin-1 in precancerous lesions of the pancreas. Nat Commun. 2025 Aug 2;16(1):7094. doi: 10.1038/s41467-025-62299-4.