ArticleCancer discovery2025
Neuro-Mesenchymal Interaction Mediated by a β2-Adrenergic Nerve Growth Factor Feedforward Loop Promotes Colorectal Cancer Progression.
Article in Cancer discovery, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 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
56 citing papers in PubMed.
- Targeting cancer-associated fibroblasts: therapeutic strategies, translational challenges, and future perspectives.Journal of hematology & oncology · 2026Review
- Cancer Neuroscience: From Local Neuro-Immune Microenvironments to Systemic Brain-Body Circuitry.MedComm · 2026Review
- Targeting the nervous system: Mechanistic insights into neuro-tumor communication and therapeutic opportunities.Acta pharmaceutica Sinica. B · 2026Review
- Article
- Neural regulation of cancer: from microenvironmental hijacking to systemic circuit co-option.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Neural regulation of tumor immunity: emerging opportunities to enhance cancer immunotherapy.Experimental & molecular medicine · 2026Review
- Electroacupuncture enhances anti-tumor immunity in TNBC by reducing NE release and blocking α2-AR-mediated NGF/Hippo signaling.Chinese medicine · 2026Article
- Stromal Regulation of Tumor Perineural Invasion: A Multicellular and Neuro-Ecological Perspective.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Neural cues differentially modulate colorectal cancer cell behavior depending on patients' genomic background.iScience · 2026Article
- Article
- Neuron-tumor interplay in colorectal cancer: from mechanisms of onset and progression to targeted therapies.Cell communication and signaling : CCS · 2026Review
- Sensory neuron-derived CCL5 orchestrates an immunosuppressive niche via regulatory T cells to fuel head and neck tumor progression.Journal for immunotherapy of cancer · 2026Article
- Disrupting sympathetic nerve-tumor crosstalk via biomimetic nanovesicles to augment chemotherapy efficacy under chronic stress.Nature communications · 2026Article
- Neuro-immune interactions in gastrointestinal oncology: Mechanisms, challenges, and therapeutic potential.Innovation (Cambridge (Mass.)) · 2026Review
- Unraveling the nexus in the neuro-neoplastic progression of colorectal cancer: Potential role of β2-adrenergic receptor (β2-AR).Journal of advanced research · 2026Review
- Myofibroblasts Induce Neuroplasticity to Promote Pancreatic Inflammation and Cancer Progression.Cancer discovery · 2026Article
- Article
- 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
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors.
Funding
Abstract
abstractCancer-associated fibroblasts (CAF) and nerves, components of the tumor microenvironment, have each been shown to directly promote gastrointestinal cancers. However, it remains unknown whether these cells interact with each other to regulate cancer progression. We found that in colorectal cancer, norepinephrine induces ADRB2 (β2-adrenergic receptor)–dependent nerve growth factor (NGF) secretion from CAFs, which in turn increases intratumor sympathetic innervation and norepinephrine accumulation. Adrenergic stimulation accelerates colorectal cancer growth through ADRA2A/Gi-mediated activation of Yes-associated protein (YAP). NGF from CAFs directly enhances colorectal cancer cell growth via the phosphatidylinositol-3-kinase/AKT pathway. Treatment with a tropomyosin receptor kinase (TRK) inhibitor decreased YAP and AKT activation and colorectal cancer progression in mice. In human colorectal cancer, high NGF expression is associated with mesenchymal-like tumor subtype and poor patient survival. These findings suggest a central role for reciprocal CAF–nerve cross-talk in promoting colorectal cancer progression. Blocking this feedforward loop with a TRK inhibitor may represent a potential therapeutic approach for colorectal cancer. SIGNIFICANCE: Our work demonstrates that the bidirectional interplay between sympathetic nerves and NGF-expressing CAFs drives colorectal tumorigenesis. This study also offers novel mechanistic insights into catecholamine action in colorectal cancer. Inhibiting the neuro-mesenchymal interaction by TRK blockade could be a potential strategy for treating colorectal cancer.
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.