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  Combined inhibition of AXL, Lyn and p130Cas kinases block migration of triple negative breast cancer cells

Penzes, K., Baumann, C., Szabadkai, I., Orfi, L., Keri, G., Ullrich, A., et al. (2014). Combined inhibition of AXL, Lyn and p130Cas kinases block migration of triple negative breast cancer cells. CANCER BIOLOGY & THERAPY, 15(11), 1571-1582. doi:10.4161/15384047.2014.956634.

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Penzes, Kinga1, Autor           
Baumann, Christine1, Autor           
Szabadkai, Istvan2, Autor
Orfi, Laszlo2, Autor
Keri, Gyoergy2, Autor
Ullrich, Axel1, Autor           
Torka, Robert1, Autor           
Affiliations:
1Ullrich, Axel / Molecular Biology, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565172              
2external, ou_persistent22              

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Schlagwörter: RECEPTOR TYROSINE KINASES; MESENCHYMAL TRANSITION; THERAPEUTIC TARGET; TUMOR-GROWTH; METASTASIS; SURVIVAL; SRC; BOSUTINIB; APOPTOSIS; PATHWAYAXL; breast cancer; Lyn; migration; migration related kinases; p130Cas; tyrosine kinase inhibitors;
 Zusammenfassung: Blocking the migration of metastatic cancer cells is a major goal in the therapy of cancer. The receptor tyrosine kinase AXL is one of the main triggers for cancer cell migration in neoplasia of breast, colon, skin, thyroid and prostate. In our study we analyzed the effect of AXL inhibition on cell motility and viability in triple negative breast cancer cell lines overexpressing AXL. Thereby we reveal that the compound BMS777607, exhibiting the lowest IC50 values for inhibition of AXL kinase activity in the studied cell lines, attenuates cell motility to a lower extent than the kinase inhibitors MPCD84111 and SKI606. By analyzing the target kinases of MPCD84111 and SKI606 with kinase profiling assays we identified Lyn, a Src family kinase, as a target of both compounds. Knockdown of Lyn and the migration-related CRK-associated substrate (p130Cas), had a significant inhibitory effect on cell migration. Taken together, our findings highlight the importance of combinatorial or multikinase inhibition of non-receptor tyrosine kinases and AXL receptor tyrosine kinase in the therapy of triple negative breast cancer.

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Sprache(n): eng - English
 Datum: 2014
 Publikationsstatus: Erschienen
 Seiten: 12
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: ISI: 000348381900014
DOI: 10.4161/15384047.2014.956634
 Art des Abschluß: -

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Titel: CANCER BIOLOGY & THERAPY
Genre der Quelle: Zeitschrift
 Urheber:
Affiliations:
Ort, Verlag, Ausgabe: 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA : TAYLOR & FRANCIS INC
Seiten: - Band / Heft: 15 (11) Artikelnummer: - Start- / Endseite: 1571 - 1582 Identifikator: ISSN: 1538-4047