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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2018
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.
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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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