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.Oncogene advance online publication, 23 October 2017; doi:10.1038/onc.2017.358.

FAM49B, a novel regulator of mitochondrial function and integrity that suppresses tumor metastasis

MS Chattaragada;C Riganti;M Sassoe;M Principe;C Roux;C Curcio;P Cappello;F Novelli
Last
2018-01-01

Abstract

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.Oncogene advance online publication, 23 October 2017; doi:10.1038/onc.2017.358.
37
6
679
709
MS Chattaragada; C Riganti; M Sassoe; M Principe; MM Santamorena; C Roux; C Curcio; A Evangelista; P Allavena; R Salvia; B Rusev; A Scarpa; P Cappello; F Novelli
File in questo prodotto:
File Dimensione Formato  
Chattagarada, Oncogene MS and Supporting, 2018.pdf

Accesso aperto

Descrizione: Chattagarada, MS and Supporting information, 2018
Tipo di file: PDF EDITORIALE
Dimensione 11.09 MB
Formato Adobe PDF
11.09 MB Adobe PDF Visualizza/Apri
Chattaragada et al_Oncogene_2017.pdf

Accesso riservato

Tipo di file: PDF EDITORIALE
Dimensione 4.53 MB
Formato Adobe PDF
4.53 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1660511
Citazioni
  • ???jsp.display-item.citation.pmc??? 27
  • Scopus 38
  • ???jsp.display-item.citation.isi??? 37
social impact