ArticleNature communications2019
c-Met activation leads to the establishment of a TGFβ-receptor regulatory network in bladder cancer progression.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 41 papers.
What it found
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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.
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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
41 citing papers in PubMed, 65 citations in OpenAlex.
- C-MET tyrosine kinase receptor: mechanisms, clinical applications and future perspectives in cancer therapy.Signal transduction and targeted therapy · 2026Review
- MEK inhibitor mirdametinib promotes fracture healing in osteofibrous dysplasia RASopathy.The Journal of clinical investigation · 2026Article
- MET signaling drives acquired resistance to erdafitinib in muscle-invasive bladder cancer cells.Cell death & disease · 2025Article
- A new 1,2,3-triazole-indirubin hybrid suppresses tumor growth and pulmonary metastasis by mitigating the HGF/c-MET axis in hepatocellular carcinoma.Journal of advanced research · 2025Article
- Sarcomatoid areas of urothelial carcinoma are enriched for CD163-positive antigen-presenting cells.The journal of pathology. Clinical research · 2025Article
- Loss of YTHDC1 mExperimental & molecular medicine · 2025Article
- Review
- Betaglycan sustains HGF/Met signaling in lung cancer and endothelial cells promoting cell migration and tumor growth.Heliyon · 2024Article
- Epithelial-to-mesenchymal transition in cancer progression: unraveling the immunosuppressive module driving therapy resistance.Cancer metastasis reviews · 2024Review
- Long non-coding RNAs: regulators of autophagy and potential biomarkers in therapy resistance and urological cancers.Frontiers in pharmacology · 2024Review
- Antithrombotic therapy for a case report of acute myocardial infarction after laparoscopic radical cystectomy.Frontiers in pharmacology · 2024Article
- SHP2 inhibitors maintain TGFβ signalling through SMURF2 inhibition.NPJ precision oncology · 2023Article
- EMT-induced immune evasion: connecting the dots from mechanisms to therapy.Clinical and experimental medicine · 2023Review
- Pesticides and Bladder Cancer: Mechanisms Leading to Anti-Cancer Drug Chemoresistance and New Chemosensitization Strategies.International journal of molecular sciences · 2023Review
- Construction of a risk model and prediction of prognosis and immunotherapy based on cuproptosis-related LncRNAs in the urinary system pan-cancer.European journal of medical research · 2023Article
- Article
- ASAP2 interrupts c-MET-CIN85 interaction to sustain HGF/c-MET-induced malignant potentials in hepatocellular carcinoma.Experimental hematology & oncology · 2023Article
- Development of resistance to FGFR inhibition in urothelial carcinoma via multiple pathways in vitro.The Journal of pathology · 2023Article
- Targeting c-Met in the treatment of urologic neoplasms: Current status and challenges.Frontiers in oncology · 2023Review
- Identification and validation of a novel cuproptosis-related lncRNA gene signature to predict prognosis and immune response in bladder cancer.Discover oncology · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
19 authors at 7 institutions in 7 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Treatment of muscle-invasive bladder cancer remains a major clinical challenge. Aberrant HGF/c-MET upregulation and activation is frequently observed in bladder cancer correlating with cancer progression and invasion. However, the mechanisms underlying HGF/c-MET-mediated invasion in bladder cancer remains unknown. As part of a negative feedback loop SMAD7 binds to SMURF2 targeting the TGFβ receptor for degradation. Under these conditions, SMAD7 acts as a SMURF2 agonist by disrupting the intramolecular interactions within SMURF2. We demonstrate that HGF stimulates TGFβ signalling through c-SRC-mediated phosphorylation of SMURF2 resulting in loss of SMAD7 binding and enhanced SMURF2 C2-HECT interaction, inhibiting SMURF2 and enhancing TGFβ receptor stabilisation. This upregulation of the TGFβ pathway by HGF leads to TGFβ-mediated EMT and invasion. In vivo we show that TGFβ receptor inhibition prevents bladder cancer invasion. Furthermore, we make a rationale for the use of combinatorial TGFβ and MEK inhibitors for treatment of high-grade non-muscle-invasive bladder cancers.
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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.