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Crosstalk between CXCR4/ACKR3 and EGFR Signaling in Breast Cancer Cells

A better understanding of the complex crosstalk among key receptors and signaling pathways involved in cancer progression is needed to improve current therapies. We have investigated in cell models representative of the major subtypes of breast cancer (BC) the interplay between the chemokine CXCL12/...

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Autores principales: Neves, Maria, Marolda, Viviana, Mayor, Federico, Penela, Petronila
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9570020/
https://www.ncbi.nlm.nih.gov/pubmed/36233192
http://dx.doi.org/10.3390/ijms231911887
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author Neves, Maria
Marolda, Viviana
Mayor, Federico
Penela, Petronila
author_facet Neves, Maria
Marolda, Viviana
Mayor, Federico
Penela, Petronila
author_sort Neves, Maria
collection PubMed
description A better understanding of the complex crosstalk among key receptors and signaling pathways involved in cancer progression is needed to improve current therapies. We have investigated in cell models representative of the major subtypes of breast cancer (BC) the interplay between the chemokine CXCL12/CXCR4/ACKR3 and EGF receptor (EGFR) family signaling cascades. These cell lines display a high heterogeneity in expression profiles of CXCR4/ACKR3 chemokine receptors, with a predominant intracellular localization and different proportions of cell surface CXCR4+, ACKR3+ or double-positive cell subpopulations, and display an overall modest activation of oncogenic pathways in response to exogenous CXCL12 alone. Interestingly, we find that in MDA-MB-361 (luminal B subtype, Her2-overexpressing), but not in MCF7 (luminal A) or MDA-MB-231 (triple negative) cells, CXCR4/ACKR3 and EGFR receptor families share signaling components and crosstalk mechanisms to concurrently promote ERK1/2 activation, with a key involvement of the G protein-coupled receptor kinase 2 (GRK2) signaling hub and the cytosolic tyrosine kinase Src. Our findings suggest that in certain BC subtypes, a relevant cooperation between CXCR4/ACKR3 and growth factor receptors takes place to integrate concurrent signals emanating from the tumor microenvironment and foster cancer progression.
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spelling pubmed-95700202022-10-17 Crosstalk between CXCR4/ACKR3 and EGFR Signaling in Breast Cancer Cells Neves, Maria Marolda, Viviana Mayor, Federico Penela, Petronila Int J Mol Sci Article A better understanding of the complex crosstalk among key receptors and signaling pathways involved in cancer progression is needed to improve current therapies. We have investigated in cell models representative of the major subtypes of breast cancer (BC) the interplay between the chemokine CXCL12/CXCR4/ACKR3 and EGF receptor (EGFR) family signaling cascades. These cell lines display a high heterogeneity in expression profiles of CXCR4/ACKR3 chemokine receptors, with a predominant intracellular localization and different proportions of cell surface CXCR4+, ACKR3+ or double-positive cell subpopulations, and display an overall modest activation of oncogenic pathways in response to exogenous CXCL12 alone. Interestingly, we find that in MDA-MB-361 (luminal B subtype, Her2-overexpressing), but not in MCF7 (luminal A) or MDA-MB-231 (triple negative) cells, CXCR4/ACKR3 and EGFR receptor families share signaling components and crosstalk mechanisms to concurrently promote ERK1/2 activation, with a key involvement of the G protein-coupled receptor kinase 2 (GRK2) signaling hub and the cytosolic tyrosine kinase Src. Our findings suggest that in certain BC subtypes, a relevant cooperation between CXCR4/ACKR3 and growth factor receptors takes place to integrate concurrent signals emanating from the tumor microenvironment and foster cancer progression. MDPI 2022-10-06 /pmc/articles/PMC9570020/ /pubmed/36233192 http://dx.doi.org/10.3390/ijms231911887 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Neves, Maria
Marolda, Viviana
Mayor, Federico
Penela, Petronila
Crosstalk between CXCR4/ACKR3 and EGFR Signaling in Breast Cancer Cells
title Crosstalk between CXCR4/ACKR3 and EGFR Signaling in Breast Cancer Cells
title_full Crosstalk between CXCR4/ACKR3 and EGFR Signaling in Breast Cancer Cells
title_fullStr Crosstalk between CXCR4/ACKR3 and EGFR Signaling in Breast Cancer Cells
title_full_unstemmed Crosstalk between CXCR4/ACKR3 and EGFR Signaling in Breast Cancer Cells
title_short Crosstalk between CXCR4/ACKR3 and EGFR Signaling in Breast Cancer Cells
title_sort crosstalk between cxcr4/ackr3 and egfr signaling in breast cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9570020/
https://www.ncbi.nlm.nih.gov/pubmed/36233192
http://dx.doi.org/10.3390/ijms231911887
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