FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W196646593> ?p ?o ?g. }

• W196646593 endingPage "e14609" @default.
• W196646593 startingPage "e14609" @default.
• W196646593 abstract "e14609 Background: Integrins are commonly upregulated in tumor cells and are important regulators of invasion and metastasis. Integrin signaling is initiated upon engagement of ECM and requires Src as well as various other proteins including ILK, FAK, and paxillin. Methods: Presence of αv integrins on CRC cell lines was established by flow cytometry. CNTO 95 (10μg/ml, a monoclonal anti-αv integrin antibody; Ortho Biotech), and dasatinib (<200nM; BMS, src small molecule inhibitor) were used to study the effects of combined integrin and src inhibition on proliferation and serum-induced migration of colon cancer cell lines in vitro. Downstream signaling changes were assessed by immunoblotting for phosphorylated forms of src, FAK (Y397, Y576/577 and Y925), paxillin, GSK3β and AKT (S473) in HT29, HCT116 and RKO. Results: Proliferation was inhibited by dasatinib in HT29, HCT116, DLD1 and HCT15 in a dose-dependent manner, while RKO and SW48 were resistant. Combining CNTO 95 with dasatinib further inhibited proliferation in all dasatinib-sensitive cells, yet resistant cells were unaffected. Migration was blocked by both CNTO 95 and dasatinib in all cell lines, and combining the two drugs produced augmented effect. Src activation and src- dependent FAK phosphorylation at sites 576 and 925 were blocked by dasatinib; CNTO 95 had little effect alone, but potentiated the effect of dasatinib. Paxillin phosphorylation was modestly blocked by both compounds, but the combination produced significantly augmented inhibition in the three cell lines tested. The phosphorylation status of AKT and GSK-3β, which are downstream of ILK, was inhibited by both drugs as single agents. The combination of dasatinib and CNTO 95 produced further inhibition. Conclusions: Dual inhibition of Src by dasatinib and αv integrins by CNTO 95 produced additive to synergistic inhibition of proliferation in dasatinib sensitive CRC cell lines, and inhibition of migration in all cell lines tested. Decreased phospho-paxillin levels may be responsible for the pronounced inhibition of migration observed after dual treatment with dasatinib and CNTO 95 in these CRC cell lines. These data support the rationale for combined Src/integrin inhibition in colon cancer, and further suggest approaches to patient selection strategies. [Table: see text]" @default.
• W196646593 created "2016-06-24" @default.
• W196646593 creator A5002665734 @default.
• W196646593 creator A5011289974 @default.
• W196646593 creator A5044586794 @default.
• W196646593 creator A5046311492 @default.
• W196646593 creator A5056139696 @default.
• W196646593 creator A5066052401 @default.
• W196646593 date "2009-05-20" @default.
• W196646593 modified "2023-09-26" @default.
• W196646593 title "Dual inhibition of αV integrins and Src kinase activity in colon cancer cells" @default.
• W196646593 doi "https://doi.org/10.1200/jco.2009.27.15_suppl.e14609" @default.
• W196646593 hasPublicationYear "2009" @default.
• W196646593 type Work @default.
• W196646593 sameAs 196646593 @default.
• W196646593 citedByCount "0" @default.
• W196646593 crossrefType "journal-article" @default.
• W196646593 hasAuthorship W196646593A5002665734 @default.
• W196646593 hasAuthorship W196646593A5011289974 @default.
• W196646593 hasAuthorship W196646593A5044586794 @default.
• W196646593 hasAuthorship W196646593A5046311492 @default.
• W196646593 hasAuthorship W196646593A5056139696 @default.
• W196646593 hasAuthorship W196646593A5066052401 @default.
• W196646593 hasConcept C108636557 @default.
• W196646593 hasConcept C116581196 @default.
• W196646593 hasConcept C11960822 @default.
• W196646593 hasConcept C137738243 @default.
• W196646593 hasConcept C1491633281 @default.
• W196646593 hasConcept C151166631 @default.
• W196646593 hasConcept C185592680 @default.
• W196646593 hasConcept C195687474 @default.
• W196646593 hasConcept C2779536868 @default.
• W196646593 hasConcept C2779976819 @default.
• W196646593 hasConcept C42362537 @default.
• W196646593 hasConcept C502942594 @default.
• W196646593 hasConcept C55493867 @default.
• W196646593 hasConcept C62112901 @default.
• W196646593 hasConcept C62478195 @default.
• W196646593 hasConcept C71924100 @default.
• W196646593 hasConcept C75217442 @default.
• W196646593 hasConcept C86803240 @default.
• W196646593 hasConcept C95444343 @default.
• W196646593 hasConceptScore W196646593C108636557 @default.
• W196646593 hasConceptScore W196646593C116581196 @default.
• W196646593 hasConceptScore W196646593C11960822 @default.
• W196646593 hasConceptScore W196646593C137738243 @default.
• W196646593 hasConceptScore W196646593C1491633281 @default.
• W196646593 hasConceptScore W196646593C151166631 @default.
• W196646593 hasConceptScore W196646593C185592680 @default.
• W196646593 hasConceptScore W196646593C195687474 @default.
• W196646593 hasConceptScore W196646593C2779536868 @default.
• W196646593 hasConceptScore W196646593C2779976819 @default.
• W196646593 hasConceptScore W196646593C42362537 @default.
• W196646593 hasConceptScore W196646593C502942594 @default.
• W196646593 hasConceptScore W196646593C55493867 @default.
• W196646593 hasConceptScore W196646593C62112901 @default.
• W196646593 hasConceptScore W196646593C62478195 @default.
• W196646593 hasConceptScore W196646593C71924100 @default.
• W196646593 hasConceptScore W196646593C75217442 @default.
• W196646593 hasConceptScore W196646593C86803240 @default.
• W196646593 hasConceptScore W196646593C95444343 @default.
• W196646593 hasIssue "15_suppl" @default.
• W196646593 hasLocation W1966465931 @default.
• W196646593 hasOpenAccess W196646593 @default.
• W196646593 hasPrimaryLocation W1966465931 @default.
• W196646593 hasRelatedWork W196646593 @default.
• W196646593 hasRelatedWork W1984942174 @default.
• W196646593 hasRelatedWork W1993878658 @default.
• W196646593 hasRelatedWork W2023991830 @default.
• W196646593 hasRelatedWork W2120324368 @default.
• W196646593 hasRelatedWork W2127699932 @default.
• W196646593 hasRelatedWork W2160839395 @default.
• W196646593 hasRelatedWork W2172014045 @default.
• W196646593 hasRelatedWork W2314941361 @default.
• W196646593 hasRelatedWork W4247056331 @default.
• W196646593 hasVolume "27" @default.
• W196646593 isParatext "false" @default.
• W196646593 isRetracted "false" @default.
• W196646593 magId "196646593" @default.
• W196646593 workType "article" @default.