English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  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.

Item is

Files

show Files

Locators

show

Creators

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

Content

show
hide
Free keywords: 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;
 Abstract: 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.

Details

show
hide
Language(s): eng - English
 Dates: 2014
 Publication Status: Published in print
 Pages: 12
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: CANCER BIOLOGY & THERAPY
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA : TAYLOR & FRANCIS INC
Pages: - Volume / Issue: 15 (11) Sequence Number: - Start / End Page: 1571 - 1582 Identifier: ISSN: 1538-4047