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A CREB3-regulated ER-Golgi trafficking signature promotes metastatic progression in breast cancer
In order to better understand the process of breast cancer metastasis, we have generated a mammary epithelial progression series of increasingly aggressive cell lines that metastasize to lung. Here, we demonstrate that up-regulation of an Endoplasmic Reticulum (ER) to Golgi trafficking gene signatur...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5844805/ https://www.ncbi.nlm.nih.gov/pubmed/29249802 http://dx.doi.org/10.1038/s41388-017-0023-0 |
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author | Howley, Breege V Link, Laura A Grelet, Simon El-Sabban, Maya Howe, Philip H |
author_facet | Howley, Breege V Link, Laura A Grelet, Simon El-Sabban, Maya Howe, Philip H |
author_sort | Howley, Breege V |
collection | PubMed |
description | In order to better understand the process of breast cancer metastasis, we have generated a mammary epithelial progression series of increasingly aggressive cell lines that metastasize to lung. Here, we demonstrate that up-regulation of an Endoplasmic Reticulum (ER) to Golgi trafficking gene signature in metastatic cells enhances transport kinetics, which promotes malignant progression. We observe increased ER-Golgi trafficking, an altered secretome and sensitivity to the retrograde transport inhibitor brefeldin A (BFA) in cells that metastasize to lung. CREB3 was identified as a transcriptional regulator of up-regulated ER-Golgi trafficking genes ARF4, COPB1 and USO1, and silencing of these genes attenuated the metastatic phenotype in vitro and lung colonization in vivo. Furthermore, high trafficking gene expression significantly correlated with increased risk of distant metastasis and reduced relapse-free and overall survival in breast cancer patients, suggesting that modulation of ER-Golgi trafficking plays an important role in metastatic progression. |
format | Online Article Text |
id | pubmed-5844805 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
record_format | MEDLINE/PubMed |
spelling | pubmed-58448052018-06-18 A CREB3-regulated ER-Golgi trafficking signature promotes metastatic progression in breast cancer Howley, Breege V Link, Laura A Grelet, Simon El-Sabban, Maya Howe, Philip H Oncogene Article In order to better understand the process of breast cancer metastasis, we have generated a mammary epithelial progression series of increasingly aggressive cell lines that metastasize to lung. Here, we demonstrate that up-regulation of an Endoplasmic Reticulum (ER) to Golgi trafficking gene signature in metastatic cells enhances transport kinetics, which promotes malignant progression. We observe increased ER-Golgi trafficking, an altered secretome and sensitivity to the retrograde transport inhibitor brefeldin A (BFA) in cells that metastasize to lung. CREB3 was identified as a transcriptional regulator of up-regulated ER-Golgi trafficking genes ARF4, COPB1 and USO1, and silencing of these genes attenuated the metastatic phenotype in vitro and lung colonization in vivo. Furthermore, high trafficking gene expression significantly correlated with increased risk of distant metastasis and reduced relapse-free and overall survival in breast cancer patients, suggesting that modulation of ER-Golgi trafficking plays an important role in metastatic progression. 2017-12-18 2018-03 /pmc/articles/PMC5844805/ /pubmed/29249802 http://dx.doi.org/10.1038/s41388-017-0023-0 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Howley, Breege V Link, Laura A Grelet, Simon El-Sabban, Maya Howe, Philip H A CREB3-regulated ER-Golgi trafficking signature promotes metastatic progression in breast cancer |
title | A CREB3-regulated ER-Golgi trafficking signature promotes metastatic progression in breast cancer |
title_full | A CREB3-regulated ER-Golgi trafficking signature promotes metastatic progression in breast cancer |
title_fullStr | A CREB3-regulated ER-Golgi trafficking signature promotes metastatic progression in breast cancer |
title_full_unstemmed | A CREB3-regulated ER-Golgi trafficking signature promotes metastatic progression in breast cancer |
title_short | A CREB3-regulated ER-Golgi trafficking signature promotes metastatic progression in breast cancer |
title_sort | creb3-regulated er-golgi trafficking signature promotes metastatic progression in breast cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5844805/ https://www.ncbi.nlm.nih.gov/pubmed/29249802 http://dx.doi.org/10.1038/s41388-017-0023-0 |
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