ArticleEMBO molecular medicine2012
Nardilysin and ADAM proteases promote gastric cancer cell growth by activating intrinsic cytokine signalling via enhanced ectodomain shedding of TNF-α.
Article in EMBO molecular medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 45 citations in OpenAlex.
- Nardilysin: classical functions and new horizons in autoimmunity.Frontiers in immunology · 2026Review
- Proteomics characterization of triple-negative apocrine carcinoma reveals molecular features of progression and chemotherapy response.Scientific reports · 2025Article
- Review
- Article
- Auxiliary roles of nardilysin in the early diagnosis of acute coronary syndrome: a prospective cohort study, the Nardi-ACS study.Internal and emergency medicine · 2024Article
- LncRNA H19 Promotes Gastric Cancer Metastasis via miR-148-3p/SOX-12 Axis.Analytical cellular pathology (Amsterdam) · 2024Article
- Immunohistochemical and clinicopathological study regarding nardilysin on extramammary Paget's disease.Archives of dermatological research · 2023Article
- Serum Nardilysin as a Prognostic Biomarker in Pancreatic Ductal Adenocarcinoma.Journal of clinical medicine · 2022Article
- Review
- Transmembrane TNF and Its Receptors TNFR1 and TNFR2 in Mycobacterial Infections.International journal of molecular sciences · 2021Review
- Review
- CagA orchestrates eEF1A1 and PKCδ to induce interleukin-6 expression inGut pathogens · 2020Article
- Nardilysin controls intestinal tumorigenesis through HDAC1/p53-dependent transcriptional regulation.JCI insight · 2018Article
- Insulin-like growth factor-1 activates different catalytic subunits p110 of PI3K in a cell-type-dependent manner to induce lipogenesis-dependent epithelial-mesenchymal transition through the regulation of ADAM10 and ADAM17.Molecular and cellular biochemistry · 2018Article
- When human cells meet bacteria: precision medicine for cancers using the microbiota.American journal of cancer research · 2018Review
- Genome-wide profiling of nardilysin target genes reveals its role in epigenetic regulation and cell cycle progression.Scientific reports · 2017Article
- Nardilysin promotes hepatocellular carcinoma through activation of signal transducer and activator of transcription 3.Cancer science · 2017Article
- Nardilysin regulates inflammation, metaplasia, and tumors in murine stomach.Scientific reports · 2017Article
- Therapeutic potential of ADAM17 modulation in gastric cancer through regulation of the EGFR and TNF-α signalling pathways.Molecular and cellular biochemistry · 2017Article
- Nardilysin is involved in autoimmune arthritis via the regulation of tumour necrosis factor alpha secretion.RMD open · 2017Article
Corrections and comments
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Authors and funding
18 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nardilysin (NRDc), a metalloendopeptidase of the M16 family, promotes ectodomain shedding of the precursor forms of various growth factors and cytokines by enhancing the protease activities of ADAM proteins. Here, we show the growth-promoting role of NRDc in gastric cancer cells. Analyses of clinical samples demonstrated that NRDc protein expression was frequently elevated both in the serum and cancer epithelium of gastric cancer patients. After NRDc knockdown, tumour cell growth was suppressed both in vitro and in xenograft experiments. In gastric cancer cells, NRDc promotes shedding of pro-tumour necrosis factor-alpha (pro-TNF-α), which stimulates expression of NF-κB-regulated multiple cytokines such as interleukin (IL)-6. In turn, IL-6 activates STAT3, leading to transcriptional upregulation of downstream growth-related genes. Gene silencing of ADAM17 or ADAM10, representative ADAM proteases, phenocopied the changes in cytokine expression and cell growth induced by NRDc knockdown. Our results demonstrate that gastric cancer cell growth is maintained by autonomous TNF-α-NF-κB and IL-6-STAT3 signalling, and that NRDc and ADAM proteases turn on these signalling cascades by stimulating ectodomain shedding of TNF-α.
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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.