ArticleThe Journal of clinical investigation2014
Four individually druggable MET hotspots mediate HGF-driven tumor progression.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 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.
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.
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Who cites it
32 citing papers in PubMed, 53 citations in OpenAlex.
- IL-2 family cytokines IL-9 and IL-21 differentially regulate innate and adaptive type 2 immunity in asthma.The Journal of allergy and clinical immunology · 2024Article
- MET Oncogene Targeting for Cancer Immunotherapy.International journal of molecular sciences · 2024Review
- Review
- hOA-DN30: a highly effective humanized single-arm MET antibody inducing remission of 'MET-addicted' cancers.Journal of experimental & clinical cancer research : CR · 2022Article
- The NHanceBiomedicines · 2021Article
- High-sensitive clinical diagnostic method for PTPRZ1-MET and the characteristic protein structure contributing to ligand-independent MET activation.CNS neuroscience & therapeutics · 2021Article
- State of the structure address on MET receptor activation by HGF.Biochemical Society transactions · 2021Review
- Engineering, Characterization, and Biological Evaluation of an Antibody Targeting the HGF Receptor.Frontiers in immunology · 2021Article
- Mouse models of colorectal cancer: Past, present and future perspectives.World journal of gastroenterology · 2020Review
- Phage Display Derived Monoclonal Antibodies: From Bench to Bedside.Frontiers in immunology · 2020Review
- The Function of the HGF/c-Met Axis in Hepatocellular Carcinoma.Frontiers in cell and developmental biology · 2020Review
- VHH-Photosensitizer Conjugates for Targeted Photodynamic Therapy of Met-Overexpressing Tumor Cells.Antibodies (Basel, Switzerland) · 2019Article
- MET/HGF Co-Targeting in Pancreatic Cancer: A Tool to Provide Insight into the Tumor/Stroma Crosstalk.International journal of molecular sciences · 2018Review
- A bispecific antibody strategy to target multiple type 2 cytokines in asthma.The Journal of allergy and clinical immunology · 2018Article
- Known and novel roles of the MET oncogene in cancer: a coherent approach to targeted therapy.Nature reviews. Cancer · 2018Review
- c-MET expression potentially contributes to the poor prognosis of rhabdomyosarcoma.International journal of clinical and experimental pathology · 2018Article
- MET Activation and Physical Dynamics of the Metastatic Process: The Paradigm of Cancers of Unknown Primary Origin.EBioMedicine · 2017Review
- Tumor Inhibitory Effect of IRCR201, a Novel Cross-Reactive c-Met Antibody Targeting the PSI Domain.International journal of molecular sciences · 2017Article
- Characterization and structural determination of a new anti-MET function-blocking antibody with binding epitope distinct from the ligand binding domain.Scientific reports · 2017Article
- Stroma-derived HGF drives metabolic adaptation of colorectal cancer to angiogenesis inhibitors.Oncotarget · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of MET by HGF plays a key role in tumor progression. Using a recently developed llama platform that generates human-like immunoglobulins, we selected 68 different antibodies that compete with HGF for binding to MET. HGF-competing antibodies recognized 4 distinct hotspots localized in different MET domains. We identified 1 hotspot that coincides with the known HGF β chain binding site on blades 2-3 of the SEMA domain β-propeller. We determined that a second and a third hotspot lie within blade 5 of the SEMA domain and IPT domains 2-3, both of which are thought to bind to HGF α chain. Characterization of the fourth hotspot revealed a region across the PSI-IPT 1 domains not previously associated with HGF binding. Individual or combined targeting of these hotspots effectively interrupted HGF/MET signaling in multiple cell-based biochemical and biological assays. Selected antibodies directed against SEMA blades 2-3 and the PSI-IPT 1 region inhibited brain invasion and prolonged survival in a glioblastoma multiforme model, prevented metastatic disease following neoadjuvant therapy in a triple-negative mammary carcinoma model, and suppressed cancer cell dissemination to the liver in a KRAS-mutant metastatic colorectal cancer model. These results identify multiple regions of MET responsible for HGF-mediated tumor progression, unraveling the complexity of HGF-MET interaction, and provide selective molecular tools for targeting MET activity in cancer.
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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.