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p140Cap inhibits β-Catenin in the breast cancer stem cell compartment instructing a protective anti-tumor immune response
The p140Cap adaptor protein is a tumor suppressor in breast cancer associated with a favorable prognosis. Here we highlight a function of p140Cap in orchestrating local and systemic tumor-extrinsic events that eventually result in inhibition of the polymorphonuclear myeloid-derived suppressor cell f...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10175288/ https://www.ncbi.nlm.nih.gov/pubmed/37169737 http://dx.doi.org/10.1038/s41467-023-37824-y |
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author | Salemme, Vincenzo Vedelago, Mauro Sarcinella, Alessandro Moietta, Federico Piccolantonio, Alessio Moiso, Enrico Centonze, Giorgia Manco, Marta Guala, Andrea Lamolinara, Alessia Angelini, Costanza Morellato, Alessandro Natalini, Dora Calogero, Raffaele Incarnato, Danny Oliviero, Salvatore Conti, Laura Iezzi, Manuela Tosoni, Daniela Bertalot, Giovanni Freddi, Stefano Tucci, Francesco A. De Sanctis, Francesco Frusteri, Cristina Ugel, Stefano Bronte, Vincenzo Cavallo, Federica Provero, Paolo Gai, Marta Taverna, Daniela Turco, Emilia Pece, Salvatore Defilippi, Paola |
author_facet | Salemme, Vincenzo Vedelago, Mauro Sarcinella, Alessandro Moietta, Federico Piccolantonio, Alessio Moiso, Enrico Centonze, Giorgia Manco, Marta Guala, Andrea Lamolinara, Alessia Angelini, Costanza Morellato, Alessandro Natalini, Dora Calogero, Raffaele Incarnato, Danny Oliviero, Salvatore Conti, Laura Iezzi, Manuela Tosoni, Daniela Bertalot, Giovanni Freddi, Stefano Tucci, Francesco A. De Sanctis, Francesco Frusteri, Cristina Ugel, Stefano Bronte, Vincenzo Cavallo, Federica Provero, Paolo Gai, Marta Taverna, Daniela Turco, Emilia Pece, Salvatore Defilippi, Paola |
author_sort | Salemme, Vincenzo |
collection | PubMed |
description | The p140Cap adaptor protein is a tumor suppressor in breast cancer associated with a favorable prognosis. Here we highlight a function of p140Cap in orchestrating local and systemic tumor-extrinsic events that eventually result in inhibition of the polymorphonuclear myeloid-derived suppressor cell function in creating an immunosuppressive tumor-promoting environment in the primary tumor, and premetastatic niches at distant sites. Integrative transcriptomic and preclinical studies unravel that p140Cap controls an epistatic axis where, through the upstream inhibition of β-Catenin, it restricts tumorigenicity and self-renewal of tumor-initiating cells limiting the release of the inflammatory cytokine G-CSF, required for polymorphonuclear myeloid-derived suppressor cells to exert their local and systemic tumor conducive function. Mechanistically, p140Cap inhibition of β-Catenin depends on its ability to localize in and stabilize the β-Catenin destruction complex, promoting enhanced β-Catenin inactivation. Clinical studies in women show that low p140Cap expression correlates with reduced presence of tumor-infiltrating lymphocytes and more aggressive tumor types in a large cohort of real-life female breast cancer patients, highlighting the potential of p140Cap as a biomarker for therapeutic intervention targeting the β-Catenin/ Tumor-initiating cells /G-CSF/ polymorphonuclear myeloid-derived suppressor cell axis to restore an efficient anti-tumor immune response. |
format | Online Article Text |
id | pubmed-10175288 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-101752882023-05-13 p140Cap inhibits β-Catenin in the breast cancer stem cell compartment instructing a protective anti-tumor immune response Salemme, Vincenzo Vedelago, Mauro Sarcinella, Alessandro Moietta, Federico Piccolantonio, Alessio Moiso, Enrico Centonze, Giorgia Manco, Marta Guala, Andrea Lamolinara, Alessia Angelini, Costanza Morellato, Alessandro Natalini, Dora Calogero, Raffaele Incarnato, Danny Oliviero, Salvatore Conti, Laura Iezzi, Manuela Tosoni, Daniela Bertalot, Giovanni Freddi, Stefano Tucci, Francesco A. De Sanctis, Francesco Frusteri, Cristina Ugel, Stefano Bronte, Vincenzo Cavallo, Federica Provero, Paolo Gai, Marta Taverna, Daniela Turco, Emilia Pece, Salvatore Defilippi, Paola Nat Commun Article The p140Cap adaptor protein is a tumor suppressor in breast cancer associated with a favorable prognosis. Here we highlight a function of p140Cap in orchestrating local and systemic tumor-extrinsic events that eventually result in inhibition of the polymorphonuclear myeloid-derived suppressor cell function in creating an immunosuppressive tumor-promoting environment in the primary tumor, and premetastatic niches at distant sites. Integrative transcriptomic and preclinical studies unravel that p140Cap controls an epistatic axis where, through the upstream inhibition of β-Catenin, it restricts tumorigenicity and self-renewal of tumor-initiating cells limiting the release of the inflammatory cytokine G-CSF, required for polymorphonuclear myeloid-derived suppressor cells to exert their local and systemic tumor conducive function. Mechanistically, p140Cap inhibition of β-Catenin depends on its ability to localize in and stabilize the β-Catenin destruction complex, promoting enhanced β-Catenin inactivation. Clinical studies in women show that low p140Cap expression correlates with reduced presence of tumor-infiltrating lymphocytes and more aggressive tumor types in a large cohort of real-life female breast cancer patients, highlighting the potential of p140Cap as a biomarker for therapeutic intervention targeting the β-Catenin/ Tumor-initiating cells /G-CSF/ polymorphonuclear myeloid-derived suppressor cell axis to restore an efficient anti-tumor immune response. Nature Publishing Group UK 2023-05-11 /pmc/articles/PMC10175288/ /pubmed/37169737 http://dx.doi.org/10.1038/s41467-023-37824-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Salemme, Vincenzo Vedelago, Mauro Sarcinella, Alessandro Moietta, Federico Piccolantonio, Alessio Moiso, Enrico Centonze, Giorgia Manco, Marta Guala, Andrea Lamolinara, Alessia Angelini, Costanza Morellato, Alessandro Natalini, Dora Calogero, Raffaele Incarnato, Danny Oliviero, Salvatore Conti, Laura Iezzi, Manuela Tosoni, Daniela Bertalot, Giovanni Freddi, Stefano Tucci, Francesco A. De Sanctis, Francesco Frusteri, Cristina Ugel, Stefano Bronte, Vincenzo Cavallo, Federica Provero, Paolo Gai, Marta Taverna, Daniela Turco, Emilia Pece, Salvatore Defilippi, Paola p140Cap inhibits β-Catenin in the breast cancer stem cell compartment instructing a protective anti-tumor immune response |
title | p140Cap inhibits β-Catenin in the breast cancer stem cell compartment instructing a protective anti-tumor immune response |
title_full | p140Cap inhibits β-Catenin in the breast cancer stem cell compartment instructing a protective anti-tumor immune response |
title_fullStr | p140Cap inhibits β-Catenin in the breast cancer stem cell compartment instructing a protective anti-tumor immune response |
title_full_unstemmed | p140Cap inhibits β-Catenin in the breast cancer stem cell compartment instructing a protective anti-tumor immune response |
title_short | p140Cap inhibits β-Catenin in the breast cancer stem cell compartment instructing a protective anti-tumor immune response |
title_sort | p140cap inhibits β-catenin in the breast cancer stem cell compartment instructing a protective anti-tumor immune response |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10175288/ https://www.ncbi.nlm.nih.gov/pubmed/37169737 http://dx.doi.org/10.1038/s41467-023-37824-y |
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