Phosphorylation-dependent differences in CXCR4-LASP1-AKT1 Interaction between breast cancer and chronic myeloid leukemia

GND
111838045
Affiliation
Institute of Experimental Biomedicine, University Hospital Wuerzburg, Josef-Schneider-Straße 2, 97080 Wuerzburg, Germany, butt_e@ukw.de
Butt, Elke;
Affiliation
Institute of Experimental Biomedicine, University Hospital Wuerzburg, Josef-Schneider-Straße 2, 97080 Wuerzburg, Germany, katrin.stempfle@gmx.de
Stempfle, Katrin;
Affiliation
Institute of Experimental Biomedicine, University Hospital Wuerzburg, Josef-Schneider-Straße 2, 97080 Wuerzburg, Germany, orenz@lister-esw.de
Lister, Lorenz;
Affiliation
Institute of Experimental Biomedicine, University Hospital Wuerzburg, Josef-Schneider-Straße 2, 97080 Wuerzburg, Germany, felix.wolf96@icloud.com
Wolf, Felix;
Affiliation
Institute of Experimental Biomedicine, University Hospital Wuerzburg, Josef-Schneider-Straße 2, 97080 Wuerzburg, Germany, marcella.kraft@gmx.de
Kraft, Marcella;
Affiliation
Institute of Experimental Biomedicine, University Hospital Wuerzburg, Josef-Schneider-Straße 2, 97080 Wuerzburg, Germany, andreasherrmann1995@gmail.com
Herrmann, Andreas B.;
Affiliation
Institute of Molecular Cell Biology, CMB-Center for Molecular Biomedicine, University Hospital Jena, Hans-Knöll-Straße 2, 07745 Jena, Germany, cristina.perpina_viciano@uni-wuerzburg.de
Viciano, Cristina Perpina;
Affiliation
Institute for Cardiovascular Prevention, LMU Munich, 80336 Munich, Germany, ipek.office@med.lmu.de
Weber, Christian;
GND
1107039339
Affiliation
Klinik für Innere Medizin II, Abteilung für Hämatologie und internistische Onkologie, Universitätsklinikum Jena, Am Klinikum 1, 07747 Jena, Germany, Andreas.Hochhaus@med.uni-jena.de
Hochhaus, Andreas;
GND
129357685
Affiliation
Klinik für Innere Medizin II, Abteilung für Hämatologie und internistische Onkologie, Universitätsklinikum Jena, Am Klinikum 1, 07747 Jena, Germany, Thomas.Ernst@med.uni-jena.de
Ernst, Thomas;
Affiliation
Institute of Molecular Cell Biology, CMB-Center for Molecular Biomedicine, University Hospital Jena, Hans-Knöll-Straße 2, 07745 Jena, Germany, Carsten.Hoffmann@med.uni-jena.de
Hoffmann, Carsten;
GND
129581607
Affiliation
Institute of Experimental Biomedicine, University Hospital Wuerzburg, Josef-Schneider-Straße 2, 97080 Wuerzburg, Germany, Zernecke_A@ukw.de
Zernecke, Alma;
GND
143565265
Affiliation
Klinik für Innere Medizin II, Abteilung für Hämatologie und internistische Onkologie, Universitätsklinikum Jena, Am Klinikum 1, 07747 Jena, Germany, Jochen.Frietsch@med.uni-jena.de
Frietsch, Jochen J.

The serine/threonine protein kinase AKT1 is a downstream target of the chemokine receptor4 (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 CXCR4is downregulated, thereby promoting the mobilization of progenitor cells into blood, the receptoris 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 partnerand as a promoter of the PI3K/AKT pathway. In this study, we uncovered a direct binding ofLASP1, phosphorylated at S146, to both CXCR4 and AKT1, as shown by immunoprecipitation assays,pull-down experiments, and immunohistochemistry data. In contrast, phosphorylation of LASP1at Y171 abrogated these interactions, suggesting that both LASP1 phospho-forms interact. Finally,findings demonstrating different phosphorylation patterns of LASP1 in breast cancer and chronicmyeloid leukemia may have implications for CXCR4 function and tyrosine kinase inhibitor treatment.

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