Phosphorylation-Dependent Differences in CXCR4-LASP1-AKT1 Interaction between Breast Cancer and Chronic Myeloid Leukemia

Elke Butt*, Katrin Stempfle, Lorenz Lister, Felix Wolf, Marcella Kraft, Andreas B. Herrmann, Cristina Perpina Viciano, Christian Weber, Andreas Hochhaus, Thomas Ernst, Carsten Hoffmann, Alma Zernecke, Jochen J. Frietsch

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The serine/threonine protein kinase AKT1 is a downstream target of the chemokine receptor 4 (CXCR4), and both proteins play a central role in the modulation of diverse cellular processes, including proliferation and cell survival. While in chronic myeloid leukemia (CML) the CXCR4 is downregulated, thereby promoting the mobilization of progenitor cells into blood, the receptor is highly expressed in breast cancer cells, favoring the migratory capacity of these cells. Recently, the LIM and SH3 domain protein 1 (LASP1) has been described as a novel CXCR4 binding partner and as a promoter of the PI3K/AKT pathway. In this study, we uncovered a direct binding of LASP1, phosphorylated at S146, to both CXCR4 and AKT1, as shown by immunoprecipitation assays, pull-down experiments, and immunohistochemistry data. In contrast, phosphorylation of LASP1 at Y171 abrogated these interactions, suggesting that both LASP1 phospho-forms interact. Finally, findings demonstrating different phosphorylation patterns of LASP1 in breast cancer and chronic myeloid leukemia may have implications for CXCR4 function and tyrosine kinase inhibitor treatment.

Original languageEnglish
Article number444
Number of pages19
JournalCells
Volume9
Issue number2
DOIs
Publication statusPublished - Feb 2020

Keywords

  • LASP1
  • CXCR4
  • AKT1
  • CML
  • breast cancer
  • BCR-ABL
  • PROTEIN-1 LASP1
  • CELL-MIGRATION
  • RESISTANCE
  • IMATINIB
  • LIM
  • BINDING
  • ASSOCIATION

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