ArticleMolecular cancer research : MCR2010
Imatinib upregulates compensatory integrin signaling in a mouse model of gastrointestinal stromal tumor and is more effective when combined with dasatinib.
Article in Molecular cancer research : MCR, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 36 citations in OpenAlex.
- The Duality of Collagens in Metastases of Solid Tumors.International journal of molecular sciences · 2025Review
- Myosin Light-Chain Kinase Inhibition Potentiates the Antitumor Effects of Avapritinib in PDGFRA D842V-Mutant Gastrointestinal Stromal Tumor.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
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- Multiple cell types contribute to the atherosclerotic lesion fibrous cap by PDGFRβ and bioenergetic mechanisms.Nature metabolism · 2021Article
- Identification of a Dexamethasone Mediated Radioprotection Mechanism Reveals New Therapeutic Vulnerabilities in Glioblastoma.Cancers · 2021Article
- Roles of Membrane Domains in Integrin-Mediated Cell Adhesion.International journal of molecular sciences · 2020Review
- Article
- A Novel Role of a Chemotherapeutic Agent in a Rat Model of Endotoxemia: Modulation of the STAT-3 Signaling Pathway.Inflammation · 2018Article
- Direct engagement of the PI3K pathway by mutant KIT dominates oncogenic signaling in gastrointestinal stromal tumor.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- ETV1-Positive Cells Give Rise toCancer research · 2017Article
- Imatinib and Nilotinib increase glioblastoma cell invasion via Abl-independent stimulation of p130Cas and FAK signalling.Scientific reports · 2016Article
- Receptor tyrosine kinase (c-Kit) inhibitors: a potential therapeutic target in cancer cells.Drug design, development and therapy · 2016Review
- CCR 20th Anniversary Commentary: A Genetic Mechanism of Imatinib Resistance in Gastrointestinal Stromal Tumor-Where Are We a Decade Later?Clinical cancer research : an official journal of the American Association for Cancer Research · 2015Article
- Drug repurposing identifies a synergistic combination therapy with imatinib mesylate for gastrointestinal stromal tumor.Molecular cancer therapeutics · 2014Article
- Increased KIT inhibition enhances therapeutic efficacy in gastrointestinal stromal tumor.Clinical cancer research : an official journal of the American Association for Cancer Research · 2014Article
- Crenolanib is active against models of drug-resistant FLT3-ITD-positive acute myeloid leukemia.Blood · 2013Article
- Primordial germ cells and gastrointestinal stromal tumors respond distinctly to a cKit overactivating allele.Human molecular genetics · 2013Article
- Imatinib resistance and microcytic erythrocytosis in a KitV558Δ;T669I/+ gatekeeper-mutant mouse model of gastrointestinal stromal tumor.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Integrating constitutive gene expression and chemoactivity: mining the NCI60 anticancer screen.PloS one · 2012Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Activating mutations in the Kit receptor tyrosine kinase are associated with gastrointestinal stromal tumor (GIST). Imatinib inhibits Kit and is front-line therapy for GIST. However, imatinib most often elicits a partial response or stable disease, and most GIST patients who initially respond to imatinib eventually acquire resistance. Thus, improved treatment strategies for GIST are needed. We investigated the role of Src family kinases (SFK) in tumorigenesis in a mouse model of human GIST. The SFKs Src and Lyn were active in GIST, and surprisingly, imatinib treatment stimulated their phosphorylation/activation. We show that integrin signaling activates focal adhesion kinase and, consequently, SFKs in GIST and that imatinib enhances integrin signaling, implying a role for the extracellular matrix and integrin signaling in tumor maintenance and imatinib resistance. Dasatinib, an inhibitor of SFKs and Kit, inhibited SFK and focal adhesion kinase activation in GIST but also inhibited Kit and Kit-dependent downstream signaling pathways including phosphoinositide 3-kinase and mitogen-activated protein kinase, but not signal transducer and activator of transcription (STAT) signaling. Whereas dasatinib and imatinib alone both produced a minimal histopathologic response, combination therapy improved their efficacy, leading to increased necrosis in GIST. These results highlight the importance of SFK and STAT signaling in GIST and suggest that the clinical efficacy of imatinib may be limited by the stimulation of integrin signaling.
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Registered trials
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