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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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Detalles Bibliográficos
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
Descripción
Sumario: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.