ArticleGastroenterology2019
Axon Guidance Molecules Promote Perineural Invasion and Metastasis of Orthotopic Pancreatic Tumors in Mice.
Article in Gastroenterology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers.
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Who cites it
118 citing papers in PubMed, 218 citations in OpenAlex.
- Sensory innervation shapes cancer immunotherapy efficacy and adverse events.Journal for immunotherapy of cancer · 2026Review
- Review
- Engineered Exosomes for Delivery of Mir-423-5p to Improve Radiation Sensitivity by Inhibiting MAP7D1 in Esophageal Cancer.Annals of surgical oncology · 2026Article
- KRAS/ACTN4/p65-NR2A axis mediates glutamine-glutamate metabolic coupling between schwann cells and pancreatic cancer promoting perineural invasion.Journal of advanced research · 2026Article
- Cancer Neoaxonogenesis: Mechanisms and Factors Involved in the Recruitment of Peripheral Nerves by Cancer Tissue.International journal of molecular sciences · 2026Review
- Netrin-1 Promotes Pancreatic Tumorigenesis and Innervation through NEO1.Cancer research · 2026Article
- Sympathetic nerve-fibroblast crosstalk drives nerve injury, fibroblast activation, and matrix remodeling in pancreatic cancer.JCI insight · 2026Article
- Heterocellular crosstalk and architecture of the pancreatic tumour microenvironment.Nature reviews. Cancer · 2026Review
- Extracellular Vesicle-Mediated O-GlcNAcase Transfer Drives Neuronal Necroptosis to Facilitate Gallbladder Cancer Perineural Invasion.Cancer research · 2026Article
- Construction of a SEMA3 family-based model to predict prognosis and molecular subtypes in pancreatic ductal adenocarcinoma.Discover oncology · 2026Article
- Review
- Targeting sensory nerves in the tumor microenvironment: a new vulnerability in cancer therapy.Cell communication and signaling : CCS · 2026Review
- A Novel Emerin/Nesprin-3 Interaction Mediates Nuclear Size Changes Induced by Oncogenic KRAS in Pancreatic Cancer Cells.Molecular and cellular biology · 2026Article
- Decoding Pancreatic Cancer Pain: From Tumor-Nerve Crosstalk to Targeted Analgesic Strategies.International journal of medical sciences · 2026Review
- Enteric neuro-immune-tumor ecosystem in pancreatic, colorectal, and gastric malignancies: context dependence and translational priorities.Frontiers in immunology · 2026Review
- Perineural invasion in solid tumors: biological foundations and the emerging integration of machine learning and artificial intelligence.Frontiers in oncology · 2026Review
- Development and validation of a novel nerve-related prognostic model for gastric cancer based on bulk and single-cell RNA sequencing data.BMC cancer · 2025Article
- Perineural Invasion in Pancreatic Ductal Adenocarcinoma: Recapitulating Its Importance and Defining Future Directions.United European gastroenterology journal · 2025Review
- Reprogramming neural-tumor crosstalk: emerging therapeutic dimensions and targeting strategies.Military Medical Research · 2025Review
- MYB and HIF1α crosstalk drives hypoxia-induced transcriptional reprogramming and adaptive signaling alterations in pancreatic cancer.Cancer letters · 2025Article
58 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsLittle is known about mechanisms of perineural invasion (PNI) by pancreatic ductal adenocarcinomas (PDAs) or other tumors. Annexin A2 (ANXA2) regulates secretion of SEMA3D, an axon guidance molecule, which binds and activates the receptor PLXND1 to promote PDA invasion and metastasis. We investigated whether axon guidance molecules promote PNI and metastasis by PDA cells in mice.
methodsWe performed studies in a dorsal root ganglion (DRG) invasion system, wild-type C57BL/6 mice (controls), mice with peripheral sensory neuron-specific disruption of PlxnD1 (PLAC mice), LSL-KRAS
resultsDRG cells increase the migration of PDC cells in invasion assays; knockdown of SEMA3D in PDA cells or antibody blockade of PLXND1 on DRG cells reduced this invasive activity. In mice, orthotopic tumors grown from PDA cells with knockdown of SEMA3D, and in PLAC mice, orthotopic tumors grown from PDA cells, had reduced innervation and formed fewer metastases than orthotopic tumors grown from PDA cells in control mice. Increased levels of SEMA3D and PLXND1 in human PDA specimens associated with PNI.
conclusionsDRG cells increase the migratory and invasive activities of pancreatic cancer cells, via secretion of SEMA3D by pancreatic cells and activation of PLXND1 on DRGs. Knockdown of SEMA3D and loss of neural PLXND1 reduces innervation of orthotopic PDAs and metastasis in mice. Increased levels of SEMA3D and PLXND1 in human PDA specimens associated with PNI. Strategies to disrupt the axon guidance pathway mediated by SEMA3D and PLXND1 might be developed to slow progression of PDA.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.