ArticleScientific reports2023
An mTOR feedback loop mediates the 'flare' ('rebound') response to MET tyrosine kinase inhibition.
Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed, 6 citations in OpenAlex.
- Harnessing native corticosteroid-binding globulin to treat life-threatening septic shock.Endocrinology · 2026Article
- Case Report: HGF and NF1 mutations as putative bypass mechanisms of MET inhibitor resistance in hepatocellular carcinoma: a case study.Frontiers in pharmacology · 2025Article
- The MET Oncogene: Thirty Years of Insights into Molecular Mechanisms Driving Malignancy.Pharmaceuticals (Basel, Switzerland) · 2024Article
- An Observatory for theCancers · 2023Review
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Authors and funding
6 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Targeted therapy significantly impairs tumour growth but suffers from limitations, among which the 'flare' ('rebound') effect. Among cancers driven by tyrosine kinase receptors, those relying on alterations of the MET oncogene benefit from treatment by specific inhibitors. Previously, we reported that discontinuation of MET tyrosine kinase receptor inhibition causes 'rebound' activation of the oncogene, with a post-treatment transient hyperphosphorylation phase that culminates into a dramatic increase in cancer cell proliferation. The molecular mechanisms behind the 'MET burst' after treatment cessation are unknown but critically important for patients. Here we identify a positive feedback loop mediated by the AKT/mTOR pathway leading to (a) enhanced MET translation by activating p70S6K and 4EBP1 and (b) MET hyper-phosphorylation by inactivation of the tyrosine-phosphatase PTP1B. The latter effect is due to m-TOR-driven PTP1B phosphorylation of the inhibitory residues Ser
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