title: A mitochondrial switch promotes tumor metastasis.
abstract: Metastatic progression of cancer is associated with poor outcome, and here we examine metabolic changes underlying this process. Although aerobic glycolysis is known to promote metastasis, we have now identified a different switch primarily affecting mitochondria. The switch involves overload of the electron transport chain (ETC) with preserved mitochondrial functions but increased mitochondrial superoxide production. It provides a metastatic advantage phenocopied by partial ETC inhibition, another situation associated with enhanced superoxide production. Both cases involved protein tyrosine kinases Src and Pyk2 as downstream effectors. Thus, two different events, ETC overload and partial ETC inhibition, promote superoxide-dependent tumor cell migration, invasion, clonogenicity, and metastasis. Consequently, specific scavenging of mitochondrial superoxide with mitoTEMPO blocked tumor cell migration and prevented spontaneous tumor metastasis in murine and human tumor models.
authors: Institut de Recherche Expérimentale et Clinique (IREC), Pole of Pharmacology (FATH), Université catholique de Louvain (UCL), Brussels 1200, Belgium.
authors: Paolo E
authors: PE
authors: Porporato
authors: Institut de Recherche Expérimentale et Clinique (IREC), Pole of Pharmacology (FATH), Université catholique de Louvain (UCL), Brussels 1200, Belgium.
authors: Valéry L
authors: VL
authors: Payen
authors: Institut de Recherche Expérimentale et Clinique (IREC), Pole of Pharmacology (FATH), Université catholique de Louvain (UCL), Brussels 1200, Belgium.
authors: Jhudit
authors: J
authors: Pérez-Escuredo
authors: Institut de Recherche Expérimentale et Clinique (IREC), Pole of Pharmacology (FATH), Université catholique de Louvain (UCL), Brussels 1200, Belgium.
authors: Christophe J
authors: CJ
authors: De Saedeleer
authors: Louvain Drug Research Institute (LDRI), Biomedical Magnetic Resonance Research Group (REMA), Université catholique de Louvain (UCL), Brussels 1200, Belgium.
authors: Pierre
authors: P
authors: Danhier
authors: Institut de Recherche Expérimentale et Clinique (IREC), Pole of Pharmacology (FATH), Université catholique de Louvain (UCL), Brussels 1200, Belgium.
authors: Tamara
authors: T
authors: Copetti
authors: Institut de Recherche Expérimentale et Clinique (IREC), Pole of Pharmacology (FATH), Université catholique de Louvain (UCL), Brussels 1200, Belgium.
authors: Suveera
authors: S
authors: Dhup
authors: Institut de Recherche Expérimentale et Clinique (IREC), Pole of Pharmacology (FATH), Université catholique de Louvain (UCL), Brussels 1200, Belgium.
authors: Morgane
authors: M
authors: Tardy
authors: Institut de Recherche Expérimentale et Clinique (IREC), Pole of Pharmacology (FATH), Université catholique de Louvain (UCL), Brussels 1200, Belgium.
authors: Thibaut
authors: T
authors: Vazeille
authors: Institut de Recherche Expérimentale et Clinique (IREC), Pole of Pharmacology (FATH), Université catholique de Louvain (UCL), Brussels 1200, Belgium.
authors: Caroline
authors: C
authors: Bouzin
authors: Institut de Recherche Expérimentale et Clinique (IREC), Pole of Pharmacology (FATH), Université catholique de Louvain (UCL), Brussels 1200, Belgium.
authors: Olivier
authors: O
authors: Feron
authors: URBC-NARILIS, University of Namur, Namur 5000, Belgium.
authors: Carine
authors: C
authors: Michiels
authors: Louvain Drug Research Institute (LDRI), Biomedical Magnetic Resonance Research Group (REMA), Université catholique de Louvain (UCL), Brussels 1200, Belgium.
authors: Bernard
authors: B
authors: Gallez
authors: Institut de Recherche Expérimentale et Clinique (IREC), Pole of Pharmacology (FATH), Université catholique de Louvain (UCL), Brussels 1200, Belgium. Electronic address: pierre.sonveaux@uclouvain.be.
authors: Pierre
authors: P
authors: Sonveaux
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D051418:Focal Adhesion Kinase 2 / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000556:secondary; D051379:Mice; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology; D013481:Superoxides / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D045222:Electron Transport Chain Complex Proteins; D013481:Superoxides; D051418:Focal Adhesion Kinase 2; D019061:src-Family Kinases