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Neural function of Netrin-1 in precancerous lesions of the pancreas
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Neural function of Netrin-1 in precancerous lesions of the pancreas
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Journal Article
Neural function of Netrin-1 in precancerous lesions of the pancreas
2025
Overview
The nervous system undergoes dynamic structural remodeling to infiltrate cancerous tumors, contributing to their growth and progression. Emerging evidence indicates that neuroplasticity initiates early, with nerve terminals detecting and responding to tissue changes even during precancerous stages. Notably, dense sympathetic axon sprouting has been observed around pancreatic intraepithelial neoplasia (PanIN), a common precursor lesion to pancreatic cancer. However, the molecular signals driving this early neuroplasticity and its functional consequences remain poorly understood. Here, we identify the axon guidance molecule Netrin-1 as a key factor secreted by pancreatic cells within precursor lesions of pancreatic cancer. Netrin-1 promotes sympathetic axon growth and branching through its receptor, Deleted in Colorectal Cancer (DCC). Inhibition of Netrin-1 disrupts sympathetic axon remodeling while accelerating PanIN formation and progression, driven by increased precancerous cell proliferation. Furthermore, human pancreatic tissue analysis corroborates Netrin-1 expression in precursor lesions. These findings suggest that Netrin-1-driven sympathetic neuroplasticity plays a protective role in the precancerous microenvironment by modulating local cellular dynamics, providing insights into early cancer progression.
The nervous system can influence cancer progression. Here, authors show in mouse models that Netrin-1 promotes sympathetic nerve remodeling in early pancreatic cancer lesions and has a protective effect against their progression.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 14/1
/ 14/32
/ 14/63
/ 38
/ 64
/ 64/60
/ Ablation
/ Animals
/ Cancer
/ Carcinoma in Situ - metabolism
/ Carcinoma in Situ - pathology
/ Endocrinology and metabolism
/ Female
/ Humanities and Social Sciences
/ Humans
/ Hépatology and Gastroenterology
/ Lesions
/ Male
/ Mice
/ Nerves
/ Netrin-1
/ Pancreatic Neoplasms - genetics
/ Pancreatic Neoplasms - metabolism
/ Pancreatic Neoplasms - pathology
/ Precancerous Conditions - metabolism
/ Precancerous Conditions - pathology
/ Science
