ArticleThe Journal of clinical investigation2023
Phenotype screens of murine pancreatic cancer identify a Tgf-α-Ccl2-paxillin axis driving human-like neural invasion.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 40 citations in OpenAlex.
- Decoding neuro-tumor interactions in pancreatic cancer: mechanisms, immunosuppressive networks and therapeutic opportunities.Molecular biomedicine · 2026Review
- Pathophysiology, assessment, and treatment of pain in patients with pancreatic ductal adenocarcinoma.Journal of gastroenterology · 2026Article
- Neuro-tumor interactions in peripheral tumors.Cancer metastasis reviews · 2026Review
- Targeting sensory nerves in the tumor microenvironment: a new vulnerability in cancer therapy.Cell communication and signaling : CCS · 2026Review
- Lactylation-drivenTheranostics · 2026Article
- Harnessing the abscopal effect: mechanistic insights and therapeutic strategies for systemic cancer immunotherapy.Frontiers in immunology · 2026Review
- Review
- The substance P/ Neurokinin-1 receptor signaling drives perineural invasion in pancreatic ductal adenocarcinoma (PDAC).Frontiers in cell and developmental biology · 2026Article
- Anti-metastatic potential of flavonoids for the treatment of cancers: focus on epithelial-mesenchymal transition (EMT) process.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- 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
- RACK1 attenuates pancreatic tumorigenesis by suppressing acinar-to-ductal metaplasia through inflammatory signaling modulation.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Tumor Innervation: From Bystander to Emerging Therapeutic Target for Cancer.International journal of molecular sciences · 2025Review
- Tumor-infiltrating nerves: unraveling the role of cancer neuroscience in tumorigenesis, disease progression, and emerging therapies.Discover oncology · 2025Review
- Nociceptor neurons promote PDAC progression and cancer pain by interaction with cancer-associated fibroblasts and suppression of natural killer cells.Cell research · 2025Article
- Pinpointing neurons that hinder cancer treatment.Nature · 2025Article
- Targeting the NPY/NPY1R signaling axis in mutant p53-dependent pancreatic cancer impairs metastasis.Science advances · 2025Article
- Extracellular vesicles from pancreatic cancer and its tumour microenvironment promote increased Schwann cell migration.British journal of cancer · 2025Article
- Pancreatic cancer extracellular vesicles stimulate Schwann cell activation and perineural invasion in vitro via IL-8/CCL2.In vitro models · 2025Article
- Central nervous system and immune cells interactions in cancer: unveiling new therapeutic avenues.Frontiers in immunology · 2025Review
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Authors and funding
35 authors at 6 institutions in 9 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Solid cancers like pancreatic ductal adenocarcinoma (PDAC), a type of pancreatic cancer, frequently exploit nerves for rapid dissemination. This neural invasion (NI) is an independent prognostic factor in PDAC, but insufficiently modeled in genetically engineered mouse models (GEMM) of PDAC. Here, we systematically screened for human-like NI in Europe's largest repository of GEMM of PDAC, comprising 295 different genotypes. This phenotype screen uncovered 2 GEMMs of PDAC with human-like NI, which are both characterized by pancreas-specific overexpression of transforming growth factor α (TGF-α) and conditional depletion of p53. Mechanistically, cancer-cell-derived TGF-α upregulated CCL2 secretion from sensory neurons, which induced hyperphosphorylation of the cytoskeletal protein paxillin via CCR4 on cancer cells. This activated the cancer migration machinery and filopodia formation toward neurons. Disrupting CCR4 or paxillin activity limited NI and dampened tumor size and tumor innervation. In human PDAC, phospho-paxillin and TGF-α-expression constituted strong prognostic factors. Therefore, we believe that the TGF-α-CCL2-CCR4-p-paxillin axis is a clinically actionable target for constraining NI and tumor progression in PDAC.
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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.