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Cell Rep. 2014 Aug 7;8(3):754-66. doi: 10.1016/j.celrep.2014.06.043. Epub 2014 Jul 24.

A mitochondrial switch promotes tumor metastasis.

Author information

1
Institut de Recherche Expérimentale et Clinique (IREC), Pole of Pharmacology (FATH), Université catholique de Louvain (UCL), Brussels 1200, Belgium.
2
Louvain Drug Research Institute (LDRI), Biomedical Magnetic Resonance Research Group (REMA), Université catholique de Louvain (UCL), Brussels 1200, Belgium.
3
URBC-NARILIS, University of Namur, Namur 5000, Belgium.
4
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.

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.

PMID:
25066121
DOI:
10.1016/j.celrep.2014.06.043
[Indexed for MEDLINE]
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