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

Cells. 2020 Feb 14;9(2):444. doi: 10.3390/cells9020444.

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.

Keywords: AKT1; CML; CXCR4; LASP1; breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Breast Neoplasms / genetics*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cytoskeletal Proteins / metabolism*
  • Female
  • Humans
  • LIM Domain Proteins / metabolism*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Receptors, CXCR4 / metabolism*
  • Transfection

Substances

  • Adaptor Proteins, Signal Transducing
  • CXCR4 protein, human
  • Cytoskeletal Proteins
  • LASP1 protein, human
  • LIM Domain Proteins
  • Receptors, CXCR4
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt