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The IKK/NF-κB signaling pathway requires Morgana to drive breast cancer metastasis
NF-κB is a transcription factor involved in the regulation of multiple physiological and pathological cellular processes, including inflammation, cell survival, proliferation, and cancer cell metastasis. NF-κB is frequently hyperactivated in several cancers, including triple-negative breast cancer....
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5696377/ https://www.ncbi.nlm.nih.gov/pubmed/29158506 http://dx.doi.org/10.1038/s41467-017-01829-1 |
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author | Fusella, Federica Seclì, Laura Busso, Elena Krepelova, Anna Moiso, Enrico Rocca, Stefania Conti, Laura Annaratone, Laura Rubinetto, Cristina Mello-Grand, Maurizia Singh, Vijay Chiorino, Giovanna Silengo, Lorenzo Altruda, Fiorella Turco, Emilia Morotti, Alessandro Oliviero, Salvatore Castellano, Isabella Cavallo, Federica Provero, Paolo Tarone, Guido Brancaccio, Mara |
author_facet | Fusella, Federica Seclì, Laura Busso, Elena Krepelova, Anna Moiso, Enrico Rocca, Stefania Conti, Laura Annaratone, Laura Rubinetto, Cristina Mello-Grand, Maurizia Singh, Vijay Chiorino, Giovanna Silengo, Lorenzo Altruda, Fiorella Turco, Emilia Morotti, Alessandro Oliviero, Salvatore Castellano, Isabella Cavallo, Federica Provero, Paolo Tarone, Guido Brancaccio, Mara |
author_sort | Fusella, Federica |
collection | PubMed |
description | NF-κB is a transcription factor involved in the regulation of multiple physiological and pathological cellular processes, including inflammation, cell survival, proliferation, and cancer cell metastasis. NF-κB is frequently hyperactivated in several cancers, including triple-negative breast cancer. Here we show that NF-κB activation in breast cancer cells depends on the presence of the CHORDC1 gene product Morgana, a previously unknown component of the IKK complex and essential for IκBα substrate recognition. Morgana silencing blocks metastasis formation in breast cancer mouse models and this phenotype is reverted by IκBα downregulation. High Morgana expression levels in cancer cells decrease recruitment of natural killer cells in the first phases of tumor growth and induce the expression of cytokines able to attract neutrophils in the primary tumor, as well as in the pre-metastatic lungs, fueling cancer metastasis. In accordance, high Morgana levels positively correlate with NF-κB target gene expression and poor prognosis in human patients. |
format | Online Article Text |
id | pubmed-5696377 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-56963772017-11-22 The IKK/NF-κB signaling pathway requires Morgana to drive breast cancer metastasis Fusella, Federica Seclì, Laura Busso, Elena Krepelova, Anna Moiso, Enrico Rocca, Stefania Conti, Laura Annaratone, Laura Rubinetto, Cristina Mello-Grand, Maurizia Singh, Vijay Chiorino, Giovanna Silengo, Lorenzo Altruda, Fiorella Turco, Emilia Morotti, Alessandro Oliviero, Salvatore Castellano, Isabella Cavallo, Federica Provero, Paolo Tarone, Guido Brancaccio, Mara Nat Commun Article NF-κB is a transcription factor involved in the regulation of multiple physiological and pathological cellular processes, including inflammation, cell survival, proliferation, and cancer cell metastasis. NF-κB is frequently hyperactivated in several cancers, including triple-negative breast cancer. Here we show that NF-κB activation in breast cancer cells depends on the presence of the CHORDC1 gene product Morgana, a previously unknown component of the IKK complex and essential for IκBα substrate recognition. Morgana silencing blocks metastasis formation in breast cancer mouse models and this phenotype is reverted by IκBα downregulation. High Morgana expression levels in cancer cells decrease recruitment of natural killer cells in the first phases of tumor growth and induce the expression of cytokines able to attract neutrophils in the primary tumor, as well as in the pre-metastatic lungs, fueling cancer metastasis. In accordance, high Morgana levels positively correlate with NF-κB target gene expression and poor prognosis in human patients. Nature Publishing Group UK 2017-11-21 /pmc/articles/PMC5696377/ /pubmed/29158506 http://dx.doi.org/10.1038/s41467-017-01829-1 Text en © The Author(s) 2017 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/. |
spellingShingle | Article Fusella, Federica Seclì, Laura Busso, Elena Krepelova, Anna Moiso, Enrico Rocca, Stefania Conti, Laura Annaratone, Laura Rubinetto, Cristina Mello-Grand, Maurizia Singh, Vijay Chiorino, Giovanna Silengo, Lorenzo Altruda, Fiorella Turco, Emilia Morotti, Alessandro Oliviero, Salvatore Castellano, Isabella Cavallo, Federica Provero, Paolo Tarone, Guido Brancaccio, Mara The IKK/NF-κB signaling pathway requires Morgana to drive breast cancer metastasis |
title | The IKK/NF-κB signaling pathway requires Morgana to drive breast cancer metastasis |
title_full | The IKK/NF-κB signaling pathway requires Morgana to drive breast cancer metastasis |
title_fullStr | The IKK/NF-κB signaling pathway requires Morgana to drive breast cancer metastasis |
title_full_unstemmed | The IKK/NF-κB signaling pathway requires Morgana to drive breast cancer metastasis |
title_short | The IKK/NF-κB signaling pathway requires Morgana to drive breast cancer metastasis |
title_sort | ikk/nf-κb signaling pathway requires morgana to drive breast cancer metastasis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5696377/ https://www.ncbi.nlm.nih.gov/pubmed/29158506 http://dx.doi.org/10.1038/s41467-017-01829-1 |
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