Mitochondrial metabolism promotes metastatic progression.

摘要: Introduction. It is broadly accepted that tumor cells rewire metabolic fluxes in order to promote cell proliferation and resistance apoptosis. However, the specific impact of metabolism on metastatic progression still poorly characterized. Since most metastases are abnormally avid for glucose (which rationale their clinical detection using FDG-PET), it often assumed mitochondrial detrimental progression. Still, mechanistic evidence missing. In this study, we assessed contribution metastasis development. Methods. Several clones with increased invasive potential were generated following vitro (starting from human cervix adenocarcinoma SiHa cells) vivo B16F10 murine melanoma selection. A complete these characterization was performed measuring oxidative glycolytic metabolism, as well redox status mass. The cancer by use inhibitors or modulators. Results discussion. We identified a switch, corresponding an overload TCA cycle preserved functions but superoxide production, promotes metastasis. This switch provided advantage reproduced moderate OXPHOS inhibition associated increase levels. Both conditions involved protein tyrosine kinase PTK2B/Pyk2 expression Src activation downstream effectors. Coherently, blockade respiration, scavenging prevented invasion. Finally, report antioxidants specifically targeting mitochondria inhibit dissemination primary tumors mice. Conclusion. Two different events (i.e., inhibition) superoxide-dependent Overall, work demonstrates central role generation pathogenesis its prevention.