ArticleEBioMedicine2015
MET Suppresses Epithelial VEGFR2 via Intracrine VEGF-induced Endoplasmic Reticulum-associated Degradation.
Article in EBioMedicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 16 citations in OpenAlex.
- Phase II Study of Cabozantinib in Patients With Bone Metastasis.The oncologist · 2022Trial
- Real-world safety assessment of MET-targeted therapies: a pharmacovigilance analysis using the FAERS database.Drugs in context · 2026Article
- Case Report: Severe palmoplantar hyperkeratosis and pain four months post-tepotinib initiation: A hand-foot skin reaction.JAAD case reports · 2025Article
- Comprehensive management of MET tyrosine kinase inhibitor-induced peripheral edema in patients withTranslational lung cancer research · 2025Review
- Endoplasmic reticulum-associated degradation mitigates atherosclerosis by maintaining cellular homeostasis.Frontiers in physiology · 2025Review
- Article
- Regulation of VEGFR2 and AKT signaling by Musashi-2 in lung cancer.bioRxiv : the preprint server for biology · 2023Article
- Safety of Tepotinib in Patients With MET Exon 14 Skipping NSCLC and Recommendations for Management.Clinical lung cancer · 2022Article
- Exploring the Intracrine Functions of VEGF-A.Biomolecules · 2021Review
- First-in-Human Phase I Study of MP0250, a First-in-Class DARPin Drug Candidate Targeting VEGF and HGF, in Patients With Advanced Solid Tumors.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2021Article
- Article
- Article
- MP0250, a VEGF and HGF neutralizing DARPinOncotarget · 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
8 authors.
Funding
Abstract
Hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) drive cancer through their respective receptors, MET and VEGF receptor 2 (VEGFR2). VEGFR2 inhibits MET by promoting MET dephosphorylation. However, whether MET conversely regulates VEGFR2 remains unknown. Here we show that MET suppresses VEGFR2 protein by inducing its endoplasmic-reticulum-associated degradation (ERAD), via intracrine VEGF action. HGF-MET signaling in epithelial cancer cells promoted VEGF biosynthesis through PI3-kinase. In turn, VEGF and VEGFR2 associated within the ER, activating inositol-requiring enzyme 1α, and thereby facilitating ERAD-mediated depletion of VEGFR2. MET disruption upregulated VEGFR2, inducing compensatory tumor growth via VEGFR2 and MEK. However, concurrent disruption of MET and either VEGF or MEK circumvented this, enabling more profound tumor inhibition. Our findings uncover unique cross-regulation between MET and VEGFR2-two RTKs that play significant roles in tumor malignancy. Furthermore, these results suggest rational combinatorial strategies for targeting RTK signaling pathways more effectively, which has potentially important implications for cancer therapy.
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What OpenQuestion holds
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.