ArticleCell reports2023
Netrin-1 feedforward mechanism promotes pancreatic cancer liver metastasis via hepatic stellate cell activation, retinoid, and ELF3 signaling.
Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- UNC5B regulates epithelial-to-mesenchymal transition through a SRC-ZEB1 signaling axis to facilitate pancreatic cancer metastasis.Oncogene · 2026Article
- The circadian gene Dec2 promotes pancreatic cancer progression and dormancy through immune evasion.Developmental cell · 2026Article
- Article
- UNC5B activates hepatic stellate cells and promotes liver fibrosis via FAK.Cell communication and signaling : CCS · 2026Article
- Targeting the CCL5/CCR5-PI3K-AKT axis suppresses hepatic stellate cell-induced breast cancer metastasis.Cancer cell international · 2026Article
- 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
- Contribution of tumor-derived extracellular vesicles in the establishment of the pre-metastatic niche: lessons learned from past experimentations and future directions.Clinical & experimental metastasis · 2026Review
- Autocrine Netrin-1 Signaling in Hepatic Stellate Cells Drives Liver Fibrosis and Diet-Induced Metabolic Dysfunction-Associated Steatohepatitis in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Research progress on immune tolerance mechanisms in liver metastatic tumors and the "Liver-metastasis-oriented shared-mechanism therapeutic strategy" approach.Medical review (2021) · 2026Review
- Mechanistic insights into hepatic metastasis of pancreatic cancer: molecular perspectives.Translational gastroenterology and hepatology · 2026Review
- Neural function of Netrin-1 in precancerous lesions of the pancreas.Nature communications · 2025Article
- The Role of Macrophage-Derived Netrin-1 in Inflammatory Diseases.Biomolecules · 2025Review
- The role of netrin-1 in the diagnosis and prognosis of bladder pain syndrome /interstitial cystitis: a comparative study.World journal of urology · 2025Article
- Assessing Implantation Sites for Pancreatic Islet Cell Transplantation: Implications for Type 1 Diabetes Mellitus Treatment.Bioengineering (Basel, Switzerland) · 2025Review
- A stable NTN1 fluorescent reporter chicken reveals cell specific molecular signatures during optic fissure closure.Scientific reports · 2025Article
- Review
- Targeting Perineural Invasion in Pancreatic Cancer.Cancers · 2024Review
- Protocol for isolating extracellular vesicles from pancreatic cancer cells for liver metastatic niche research.STAR protocols · 2024Article
- Unveiling the cancer risk nexus of the steatotic liver.Trends in endocrinology and metabolism: TEM · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 10 institutions in 2 countries.
Funding
Abstract
The biology of metastatic pancreatic ductal adenocarcinoma (PDAC) is distinct from that of the primary tumor due to changes in cell plasticity governed by a distinct transcriptome. Therapeutic strategies that target this distinct biology are needed. We detect an upregulation of the neuronal axon guidance molecule Netrin-1 in PDAC liver metastases that signals through its dependence receptor (DR), uncoordinated-5b (Unc5b), to facilitate metastasis in vitro and in vivo. The mechanism of Netrin-1 induction involves a feedforward loop whereby Netrin-1 on the surface of PDAC-secreted extracellular vesicles prepares the metastatic niche by inducing hepatic stellate cell activation and retinoic acid secretion that in turn upregulates Netrin-1 in disseminated tumor cells via RAR/RXR and Elf3 signaling. While this mechanism promotes PDAC liver metastasis, it also identifies a therapeutic vulnerability, as it can be targeted using anti-Netrin-1 therapy to inhibit metastasis using the Unc5b DR cell death mechanism.
Indexed as
Identifiers
What OpenQuestion holds
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.