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FAM49B, a novel regulator of mitochondrial function and integrity that suppresses tumor metastasis
Mitochondrial dysregulation plays a central role in cancers and drives reactive oxygen species (ROS)-dependent tumor progression. We investigated the pro-tumoral roles of mitochondrial dynamics and altered intracellular ROS levels in pancreatic ductal adenocarcinoma (PDAC). We identified ‘family wit...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5808099/ https://www.ncbi.nlm.nih.gov/pubmed/29059164 http://dx.doi.org/10.1038/onc.2017.358 |
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author | Chattaragada, M S Riganti, C Sassoe, M Principe, M Santamorena, M M Roux, C Curcio, C Evangelista, A Allavena, P Salvia, R Rusev, B Scarpa, A Cappello, P Novelli, F |
author_facet | Chattaragada, M S Riganti, C Sassoe, M Principe, M Santamorena, M M Roux, C Curcio, C Evangelista, A Allavena, P Salvia, R Rusev, B Scarpa, A Cappello, P Novelli, F |
author_sort | Chattaragada, M S |
collection | PubMed |
description | Mitochondrial dysregulation plays a central role in cancers and drives reactive oxygen species (ROS)-dependent tumor progression. We investigated the pro-tumoral roles of mitochondrial dynamics and altered intracellular ROS levels in pancreatic ductal adenocarcinoma (PDAC). We identified ‘family with sequence similarity 49 member B’ (FAM49B) as a mitochondria-localized protein that regulates mitochondrial fission and cancer progression. Silencing FAM49B in PDAC cells resulted in increased fission and mitochondrial ROS generation, which enhanced PDAC cell proliferation and invasion. Notably, FAM49B expression levels in PDAC cells were downregulated by the tumor microenvironment. Overall, the results of this study show that FAM49B acts as a suppressor of cancer cell proliferation and invasion in PDAC by regulating tumor mitochondrial redox reactions and metabolism. |
format | Online Article Text |
id | pubmed-5808099 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-58080992018-02-14 FAM49B, a novel regulator of mitochondrial function and integrity that suppresses tumor metastasis Chattaragada, M S Riganti, C Sassoe, M Principe, M Santamorena, M M Roux, C Curcio, C Evangelista, A Allavena, P Salvia, R Rusev, B Scarpa, A Cappello, P Novelli, F Oncogene Original Article Mitochondrial dysregulation plays a central role in cancers and drives reactive oxygen species (ROS)-dependent tumor progression. We investigated the pro-tumoral roles of mitochondrial dynamics and altered intracellular ROS levels in pancreatic ductal adenocarcinoma (PDAC). We identified ‘family with sequence similarity 49 member B’ (FAM49B) as a mitochondria-localized protein that regulates mitochondrial fission and cancer progression. Silencing FAM49B in PDAC cells resulted in increased fission and mitochondrial ROS generation, which enhanced PDAC cell proliferation and invasion. Notably, FAM49B expression levels in PDAC cells were downregulated by the tumor microenvironment. Overall, the results of this study show that FAM49B acts as a suppressor of cancer cell proliferation and invasion in PDAC by regulating tumor mitochondrial redox reactions and metabolism. Nature Publishing Group 2018-02-08 2017-10-23 /pmc/articles/PMC5808099/ /pubmed/29059164 http://dx.doi.org/10.1038/onc.2017.358 Text en Copyright © 2018 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/ |
spellingShingle | Original Article Chattaragada, M S Riganti, C Sassoe, M Principe, M Santamorena, M M Roux, C Curcio, C Evangelista, A Allavena, P Salvia, R Rusev, B Scarpa, A Cappello, P Novelli, F FAM49B, a novel regulator of mitochondrial function and integrity that suppresses tumor metastasis |
title | FAM49B, a novel regulator of mitochondrial function and integrity that suppresses tumor metastasis |
title_full | FAM49B, a novel regulator of mitochondrial function and integrity that suppresses tumor metastasis |
title_fullStr | FAM49B, a novel regulator of mitochondrial function and integrity that suppresses tumor metastasis |
title_full_unstemmed | FAM49B, a novel regulator of mitochondrial function and integrity that suppresses tumor metastasis |
title_short | FAM49B, a novel regulator of mitochondrial function and integrity that suppresses tumor metastasis |
title_sort | fam49b, a novel regulator of mitochondrial function and integrity that suppresses tumor metastasis |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5808099/ https://www.ncbi.nlm.nih.gov/pubmed/29059164 http://dx.doi.org/10.1038/onc.2017.358 |
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