ArticleMolecular oncology2015
TNF-α promotes invasive growth through the MET signaling pathway.
Article in Molecular oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 47 citations in OpenAlex.
- Therapeutic responses toScience translational medicine · 2020Trial
- Conditional myeloid-specific deletion of Ube2n hinders YUMM1.7 melanoma growth.Frontiers in oncology · 2026Article
- EpCAM activates the ERK-EGR1 signaling axis and promotes TNF-α-induced the progression of anaplastic thyroid cancer.Journal of translational medicine · 2025Article
- Extracellular vesicles derived from pro-inflammatory M1 macrophages induce an inflammatory and invasive phenotype in melanoma cells.Cell communication and signaling : CCS · 2025Article
- JAK-STAT-activated, fratricide-resistant CAR-T cells targeting membrane-bound TNF effectively treat AML and solid tumors.Journal for immunotherapy of cancer · 2025Article
- Nerelimomab Alleviates Capsaicin-Induced Acute Lung Injury by Inhibiting TNF Signaling and Apoptosis.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Disease specific urinary biomarkers in the central nervous system.Scientific reports · 2023Article
- Application progress of liquid biopsy in gastric cancer.Frontiers in oncology · 2022Review
- Glucose transporters: Important regulators of endometrial cancer therapy sensitivity.Frontiers in oncology · 2022Review
- WBP2 promotes BTRC mRNA stability to drive migration and invasion in triple-negative breast cancer via NF-κB activation.Molecular oncology · 2022Article
- Personalizing first-line treatment in advanced colorectal cancer: Present status and future perspectives.Journal of clinical and translational research · 2021Review
- Mesenchymal Epithelial Transition Factor Signaling in Pediatric Nervous System Tumors: Implications for Malignancy and Cancer Stem Cell Enrichment.Frontiers in cell and developmental biology · 2021Review
- Tumor necrosis factor α inhibition overcomes immunosuppressive M2b macrophage-induced bevacizumab resistance in triple-negative breast cancer.Cell death & disease · 2020Article
- Comprehensive review of targeted therapy for colorectal cancer.Signal transduction and targeted therapy · 2020Review
- The Emerging Role of the c-MET-HGF Axis in Non-small Cell Lung Cancer Tumor Immunology and Immunotherapy.Frontiers in oncology · 2020Review
- Article
- Combined c-Met/Trk Inhibition Overcomes Resistance to CDK4/6 Inhibitors in Glioblastoma.Cancer research · 2018Article
- Lack of hepatic stimulator substance expression promotes hepatocellular carcinoma metastasis partly through ERK-activated epithelial-mesenchymal transition.Laboratory investigation; a journal of technical methods and pathology · 2018Article
- Known and novel roles of the MET oncogene in cancer: a coherent approach to targeted therapy.Nature reviews. Cancer · 2018Review
- Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The inflammatory cytokine Tumor Necrosis Factor Alpha (TNF-α) is known to trigger invasive growth, a physiological property for tissue healing, turning into a hallmark of progression in cancer. However, the invasive response to TNF-α relies on poorly understood molecular mechanisms. We thus investigated whether it involves the MET oncogene, which regulates the invasive growth program by encoding the tyrosine kinase receptor for Hepatocyte Growth Factor (HGF). Here we show that the TNF-α pro-invasive activity requires MET function, as it is fully inhibited by MET-specific inhibitors (small-molecules, antibodies, and siRNAs). Mechanistically, we show that TNF-α induces MET transcription via NF-κB, and exploits MET to sustain MEK/ERK activation and Snail accumulation, leading to E-cadherin downregulation. We then show that TNF-α not only induces MET expression in cancer cells, but also HGF secretion by fibroblasts. Consistently, we found that, in human colorectal cancer tissues, high levels of TNF-α correlates with increased expression of both MET and HGF. These findings suggest that TNF-α fosters a HGF/MET pro-invasive paracrine loop in tumors. Targeting this ligand/receptor pair would contribute to prevent cancer progression associated with inflammation.
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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.