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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...

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Detalles Bibliográficos
Autores principales: Howley, Breege V, Link, Laura A, Grelet, Simon, El-Sabban, Maya, Howe, Philip H
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2017
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.
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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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