ArticleOncogene2014
Cbl-independent degradation of Met: ways to avoid agonism of bivalent Met-targeting antibody.
Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 74 citations in OpenAlex.
- Targeting c-MET Alterations in Cancer: A Review of Genetic Drivers and Therapeutic Implications.Cancers · 2025Review
- Advances in clinical research of MET exon 14 skipping mutations in non-small cell lung cancer.Journal of cancer research and clinical oncology · 2025Review
- MET amplification correlates with poor prognosis and immunotherapy response as a subtype of melanoma: a multicenter retrospective study.BMC cancer · 2024Article
- Tumor biomarkers for diagnosis, prognosis and targeted therapy.Signal transduction and targeted therapy · 2024Review
- The MET Oncogene: Thirty Years of Insights into Molecular Mechanisms Driving Malignancy.Pharmaceuticals (Basel, Switzerland) · 2024Article
- MET exon 14 skipping mutation drives cancer progression and recurrence via activation of SMAD2 signalling.British journal of cancer · 2024Article
- Review
- An Observatory for theCancers · 2023Review
- Article
- hOA-DN30: a highly effective humanized single-arm MET antibody inducing remission of 'MET-addicted' cancers.Journal of experimental & clinical cancer research : CR · 2022Article
- Review
- Aryl Hydrocarbon Receptor Defect Attenuates Mitogen-Activated Signaling through Leucine-Rich Repeats and Immunoglobulin-like Domains 1 (LRIG1)-Dependent EGFR Degradation.International journal of molecular sciences · 2021Article
- High-Content Analysis-Based Sensitivity Prediction and Novel Therapeutics Screening for c-Met-Addicted Glioblastoma.Cancers · 2021Article
- cIRCR201-dPBD, a Novel Pyrrolobenzodiazepine Dimer-Containing Site-Specific Antibody-Drug Conjugate Targeting c-Met Overexpression Tumors.ACS omega · 2020Article
- MET and RON receptor tyrosine kinases in colorectal adenocarcinoma: molecular features as drug targets and antibody-drug conjugates for therapy.Journal of experimental & clinical cancer research : CR · 2020Review
- MET targeting: time for a rematch.Oncogene · 2020Review
- A Review of Papillary Renal Cell Carcinoma and MET Inhibitors.Kidney cancer (Clifton, Va.) · 2019Review
- MET Genomic Alterations in Head and Neck Squamous Cell Carcinoma (HNSCC): Rapid Response to Crizotinib in a Patient with HNSCC with a NovelThe oncologist · 2019Article
- Induction of MET Receptor Tyrosine Kinase Down-regulation through Antibody-mediated Receptor Clustering.Scientific reports · 2019Article
- Exploratory analysis of introducing next-generation sequencing-based method to treatment-naive lung cancer patients.Journal of thoracic disease · 2018Article
Corrections and comments
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Authors and funding
17 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Met receptor tyrosine kinase, found to be constitutively activated in many tumors, has become a leading target for cancer therapy. Disruptions in Met downregulation have been associated with aggressive tumor progression with several therapeutic strategies addressing this aspect of Met biology. Castias B-lineage lymphoma (Cbl) E3 ligase-mediated degradation, which attenuates Met signaling via ligand-dependent Met internalization, is a major negative regulator of Met expression. It is believed that one of the mechanisms by which the therapeutic anti-Met antibodies induce cancer cell death in Met overexpressing tumors is via internalization and subsequent degradation of Met from the cell surface. However, a previously reported Met-targeting antibody demonstrated intrinsic agonistic activity while being capable of inducing Cbl-mediated degradation of Met, suggesting that Cbl-mediated degradation requires receptor activation and impedes therapeutic application. We have developed a potent and selective bivalent Met-targeting antibody (SAIT301) that invokes Met degradation using an alternative regulator LRIG1. In this report, we demonstrate that LRIG1 mediates degradation of Met by SAIT301 and this degradation does not require Met activation. Furthermore, SAIT301 was able to downregulate Met and dramatically inhibit growth of tumors with low or no Cbl expression, as well as tumors with Met exon 14 deletion that prevents Met binding to Cbl. In summary, we demonstrate the enhanced therapeutic potential of a novel tumor-inhibiting anti-Met antibody, SAIT301, which utilizes a Cbl-independent, LRIG1-mediated Met degradation pathway and thereby avoids the agonism that limits the effectiveness of previously reported anti-Met antibodies.
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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.