ArticleOncogene2022
Tumor innervation is triggered by endoplasmic reticulum stress.
Article in Oncogene, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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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.
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Who cites it
20 citing papers in PubMed, 26 citations in OpenAlex.
- Decoding neuro-tumor interactions in pancreatic cancer: mechanisms, immunosuppressive networks and therapeutic opportunities.Molecular biomedicine · 2026Review
- Neuro-immune crosstalk in the tumor microenvironment: mechanisms and therapeutic implications for cancer immunotherapy.Journal of neuroinflammation · 2026Review
- Molecular mechanisms and therapeutic targets in lung cancer-nerve crosstalk.Chinese medical journal pulmonary and critical care medicine · 2026Review
- Hypoxia-induced endoplasmic reticulum stress mediates lenvatinib resistance in hepatocellular carcinoma through the IRE1α-XBP1s-HIF1α pathway.Journal of cancer research and clinical oncology · 2026Article
- Review
- The neuro-vascular-immune triad: the interactive network in the tumor microenvironment.Cell communication and signaling : CCS · 2026Review
- Tumor-Induced Rewiring of Splenic Niches: from Immune Organ to Cancer Accomplice.International journal of biological sciences · 2026Review
- Peripheral Nerve-Cancer Interactions in the Tumor Microenvironment: A Three-Dimensional Framework Integrating Mechanisms, Modulators, and Therapeutic Strategies.Research (Washington, D.C.) · 2026Review
- Photothermal therapy triggering organelle stress and metabolic reprogramming to potentiate antitumor immunity.Frontiers in immunology · 2026Review
- Reprogramming neural-tumor crosstalk: emerging therapeutic dimensions and targeting strategies.Military Medical Research · 2025Review
- The neuro-immune axis in cancer: from mechanisms to therapeutic opportunities.Journal of hematology & oncology · 2025Review
- Hijacking homeostasis: the brain-body neural circuitry in tumor pathogenesis and emerging therapeutic frontiers.Molecular cancer · 2025Review
- Function and application of brain‑derived neurotrophic factor precursors (Review).International journal of molecular medicine · 2025Review
- Multiple cancer cell types release LIF and Gal3 to hijack neural signals.Cell research · 2024Article
- cAMP-PKA/EPAC signaling and cancer: the interplay in tumor microenvironment.Journal of hematology & oncology · 2024Review
- Myriad factors and pathways influencing tumor radiotherapy resistance.Open life sciences · 2024Review
- The sympathetic nervous system shapes the tumor microenvironment to impair chemotherapy response.Frontiers in oncology · 2024Review
- The Bladder Tumor Microenvironment Components That Modulate the Tumor and Impact Therapy.International journal of molecular sciences · 2023Review
- Article
- Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nerve infiltration in the tumor microenvironment is emerging as a promoter of cancer progression that could be targeted in therapies, but the mechanisms initiating tumor innervation remain to be elucidated. Here we report that endoplasmic reticulum (ER) stress in cancer cells is transmitted to neuronal cells, resulting in neurite outgrowth and tumor innervation. In vitro, the induction of ER stress in various human cancer cells resulted in the synthesis and release of the precursor for brain-derived neurotrophic factor (proBDNF) through a mechanism dependent on the transcription factor X-box binding protein 1 (XBP1). Cancer cell-released proBDNF was found to mediate the transmission of ER stress to neurons, resulting in the stimulation of neurite outgrowth. Next-generation sequencing indicated the increased expression of the Egl-9 family hypoxia inducible factor 3 (EGLN3) that was mediated by c-MYC and necessary to neurite outgrowth induced by proBDNF. In orthotopic tumor xenograft, ER stress stimulated XBP1 and proBDNF expression as well as tumor innervation. Anti-proBDNF antibody inhibited both tumor innervation and cancer progression induced by ER stress. Interestingly, the chemotherapeutic drug 5-Fluorouracil (5-FU) was found to induce ER stress and tumor innervation, and this effect was inhibited by anti-proBDNF antibody. Finally, in human tumors, cancer tissues with nerve infiltration expressed high XBP1 and proBDNF while EGLN3 was upregulated in infiltrated nerves. This study reveals that ER stress participates in tumor innervation through the release of proBDNF and that targeting this pathway could be used in future therapies.
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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.