ArticleOncogene2023
Stromal nicotinamide N-methyltransferase orchestrates the crosstalk between fibroblasts and tumour cells in oral squamous cell carcinoma: evidence from patient-derived assembled organoids.
Article in Oncogene, 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, 31 citations in OpenAlex.
- CEBPG-Mediated Palmitic Acid Adaptation of Cancer-Associated Fibroblasts Drives Metastasis of Oral Squamous Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- NNMT and the methylation sink: integrating metabolism, epigenetics and immunity in cancer.BMC medicine · 2026Review
- Colony-stimulating factor-2 triggers NNMT-dependent myofibroblast activation in head and neck cancer.Oncogene · 2026Article
- A human patient-derived organoid biobank to model tumor heterogeneity and therapeutic vulnerability for oral squamous cell carcinoma.Cell reports. Medicine · 2026Article
- [Research and application progress of organoids in head and neck squamous cell carcinoma].Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery · 2026Review
- Unraveling the impact of cancer-associated fibroblasts on lymphatic metastasis of head and neck squamous cell carcinoma.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Quinazolinone derivatives as potential anti‑tumor agents: Structural features and molecular mechanisms in inducing cell death (Review).International journal of molecular medicine · 2025Review
- Head and neck cancer organoids: a panoramic perspective from basic construction to clinical translation.Stem cell research & therapy · 2025Review
- Article
- Exploring Cancer-Associated Fibroblasts in OSCC and OPMDs: Microenvironment Insights. Scoping Review.Oral diseases · 2025Article
- Article
- Nicotinamide N-methyltransferase negatively regulates metastasis-promoting property of cancer-associated fibroblasts in lung adenocarcinoma.Cancer communications (London, England) · 2025Article
- Facilitation of Tumor Stroma-Targeted Therapy: Model Difficulty and Co-Culture Organoid Method.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Biomedical applications of organoids derived from the digestive system.Frontiers in cell and developmental biology · 2025Review
- Organoid Technology in Precision Medicine for Head and Neck Cancer.Oncology research · 2025Review
- Exploring NNMT: from metabolic pathways to therapeutic targets.Archives of pharmacal research · 2024Review
- NNMT switches the proangiogenic phenotype of cancer-associated fibroblasts via epigenetically regulating ETS2/VEGFA axis.Oncogene · 2024Article
- Lactate-driven type I collagen deposition facilitates cancer stem cell-like phenotype of head and neck squamous cell carcinoma.iScience · 2024Article
- Stromal thrombospondin 1 suppresses angiogenesis in oral submucous fibrosis.International journal of oral science · 2024Article
- Tumor microenvironment in oral squamous cell carcinoma.Frontiers in immunology · 2024Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nicotinamide N-methyltransferase (NNMT) has been reported to be linked to methylation reprogramming in cancer cells. However, the role of NNMT in the tumour microenvironment (TME) remains elusive. Here, we found that the expression of NNMT was elevated in the stroma of oral squamous cell carcinoma (OSCC). Using a fibroblast-attached organoids (FAOs) model, we confirmed that stromal NNMT expression contributed to the generation of assembled tumour organoids. In a tumour regeneration assay with co-implanted OSCC cells and cancer-associated fibroblasts (CAFs), the tumour-initiating activity was reduced when NNMT was silenced in CAFs. In contrast, overexpression of NNMT in paracancerous fibroblasts (PFs) accelerated tumour growth in co-inoculation experiments. Notably, fibroblast-specific NNMT can regulate type I collagen deposition in both FAOs and xenografts. Further investigations confirmed that the stromal NNMT-aggravated oncogenic activities were attenuated by treatment with inhibitors of either collagen synthesis (e.g. losartan, tranilast, and halofuginone) in fibroblasts, or the focal adhesion kinase (FAK) signal (i.e. defactinib) in cancer cells. Mechanistically, overexpression of NNMT reduced the enrichment of H3K27me3 at the promoter of the gene encoding lysyl oxidase (LOX), a key enzyme that regulates the cross-linking of collagen I. Overall, we propose that the NNMT-LOX-FAK cascade contributes to the crosstalk between cancer cells and fibroblasts during OSCC development, and that NNMT-centric extracellular matrix remodelling is a novel therapeutic target for patients with OSCC.
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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.