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

Kinga Pénzes, Christine Baumann, István Szabadkai, László Orfi, György Kéri, Axel Ullrich, Robert Torka

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1571-1582
Number of pages12
JournalCancer Biology and Therapy
Volume15
Issue number11
DOIs
Publication statusPublished - Nov 1 2014

Keywords

  • AXL
  • Breast cancer
  • Lyn
  • Migration
  • Migration related kinases
  • P130Cas
  • Tyrosine kinase inhibitors

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

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