ArticleClinical cancer research : an official journal of the American Association for Cancer Research2011
Distinct interactions between c-Src and c-Met in mediating resistance to c-Src inhibition in head and neck cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Anticancer Potential of Selected Flavonols: Fisetin, Kaempferol, and Quercetin on Head and Neck Cancers.Nutrients · 2021Pooled it
- Met Receptor Tyrosine Kinase and Chemoprevention of Oral Cancer.Journal of the National Cancer Institute · 2018Trial
- Erlotinib, erlotinib-sulindac versus placebo: a randomized, double-blind, placebo-controlled window trial in operable head and neck cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2014Trial
- Evaluation of a Novel MET-Targeting Camelid-Derived Antibody in Head and Neck Cancer.Molecular pharmaceutics · 2024Article
- Functional roles of SRC signaling in pancreatic cancer: Recent insights provide novel therapeutic opportunities.Oncogene · 2023Review
- Blockade of c-Met-Mediated Signaling Pathways by E7050 Suppresses Growth and Promotes Apoptosis in Multidrug-Resistant Human Uterine Sarcoma Cells.International journal of molecular sciences · 2022Article
- Regulation of growth, invasion and metabolism of breast ductal carcinoma through CCL2/CCR2 signaling interactions with MET receptor tyrosine kinases.Neoplasia (New York, N.Y.) · 2022Article
- Molecular mechanism(s) of regulation(s) of c-MET/HGF signaling in head and neck cancer.Molecular cancer · 2022Review
- Targeting c-Met in triple negative breast cancer: preclinical studies using the c-Met inhibitor, Cpd A.Investigational new drugs · 2020Article
- Structure and Characterization of a Covalent Inhibitor of Src Kinase.Frontiers in molecular biosciences · 2020Article
- The Differential Impact of SRC Expression on the Prognosis of Patients with Head and Neck Squamous Cell Carcinoma.Cancers · 2019Article
- Non-canonical cMet regulation by vimentin mediates Plk1 inhibitor-induced apoptosis.EMBO molecular medicine · 2019Article
- Beyond EGFR inhibition: multilateral combat strategies to stop the progression of head and neck cancer.Experimental & molecular medicine · 2019Review
- Novel genetic alterations and their impact on target therapy response in head and neck squamous cell carcinoma.Cancer management and research · 2019Review
- Phase I study of the combination of crizotinib (as a MET inhibitor) and dasatinib (as a c-SRC inhibitor) in patients with advanced cancer.Investigational new drugs · 2018Article
- Activated HGF-c-Met Axis in Head and Neck Cancer.Cancers · 2017Review
- Dual inhibition of MET and SRC kinase activity as a combined targeting strategy for colon cancer.Experimental and therapeutic medicine · 2017Article
- Mutations of the LIM protein AJUBA mediate sensitivity of head and neck squamous cell carcinoma to treatment with cell-cycle inhibitors.Cancer letters · 2017Article
- Studies on the Contribution of Cox-2 Expression in the Progression of Oral Squamous Cell Carcinoma and H-Ras Activation.Pathology oncology research : POR · 2017Article
- Cytoplasmic c-ros oncogene 1 receptor tyrosine kinase expression may be associated with the development of human oral squamous cell carcinoma.Oncology letters · 2015Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
purposec-Src inhibition in cancer cells leads to an abrogation of invasion but a variable effect on apoptosis. The pathways downstream of c-Src promoting survival are not well characterized. Because cancer therapy that both decreases invasion and induces significant apoptosis would be ideal, we sought to characterize the mechanisms of resistance to c-Src inhibition. EXPERIMENTAL
designc-Src was inhibited in a panel of oral cancer cell lines and subsequent survival and signaling measured. The interactions between c-Src and c-Met were evaluated using immunoprecitation and an in vitro kinase assay. Cytotoxicity was measured and the Chou-Talalay combination index calculated. An orthotopic model of oral cancer was used to assess the effects of c-Met and c-Src inhibitors.
resultsInhibition of c-Src resulted in c-Met inhibition in sensitive cells lines, but not in resistant cell lines. Isolated c-Met was a c-Src substrate in both sensitive and resistant cells, but there was no interaction of c-Src and c-Met in intact resistant cells. To examine the biological consequences of this mechanism, we demonstrated synergistic cytotoxicity, enhanced apoptosis, and decreased tumor size with the combination of c-Src and c-Met inhibitors.
conclusionsSustained c-Met activation can mediate resistance to c-Src inhibition. These data suggest that the differences between c-Met and c-Src signaling in sensitive and resistant cells are due to distinct factors promoting or inhibiting interactions, respectively, rather than to intrinsic structural changes in c-Src or c-Met. The synergistic cytotoxic effects of c-Src and c-Met inhibition may be important for the treatment of head and neck 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.