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Abstract B09: Mitochondrial respiration controlled by survivin directs mitochondrial dynamics and tumor cell invasion
Recent studies have focused on unraveling the molecular processes by which cancer cells undergo metabolic reprogramming. The switch from oxidative phosphorylation to glycolysis allows cancer cells to adapt to harsh conditions, evade cell death and perpetuate cell growth and cell invasion. Survivin,...
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Published in: | Molecular cancer research 2016-01, Vol.14 (1_Supplement), p.B09-B09 |
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Main Authors: | , , , , , , |
Format: | Article |
Language: | English |
Online Access: | Get full text |
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Summary: | Recent studies have focused on unraveling the molecular processes by which cancer cells undergo metabolic reprogramming. The switch from oxidative phosphorylation to glycolysis allows cancer cells to adapt to harsh conditions, evade cell death and perpetuate cell growth and cell invasion. Survivin, a member of the Inhibitor of Apoptosis (IAP) gene family, is multifunctional protein. Survivin plays a critical role in promoting cell proliferation by regulating cell division, and protecting cancer cells from apoptosis. Most importantly, survivin has been shown to be highly expressed in cancers, associated with poor disease outcome and metastatic dissemination. In addition, previous studies have identified a novel pool of survivin that localizes to mitochondria selectively in tumors. This pool of survivin prevents cancer cell apoptosis and contributes to tumor progression, but the underlying mechanism is uncertain. In this study, with the use of sirRNA and pharmacological approaches against survivin, as well as protein reconstitution experiments, we dissect the role of mitochondrial survivin in modulating tumor bioenergetics. Biochemically, this study identifies mitochondrial survivin as part of a multi-protein complex with mitochondrial chaperone TRAP-1 and oxidative phosphorylation Complex II subunits. Survivin recruitment to this complex ensures protein folding and oxidative phosphorylation activity. Interference with this pathway inhibits cellular respiration, ATP production and induces cellular starvation. Functionally, this multiprotein complex suppresses tumor cell migration, invasion and affects metastatic progression in vivo. Overall, this study identifies mitochondrial bioenergetics, regulated by mitochondrial survivin, as a modulator of tumor cell invasion and metastasis.
Citation Format: Dayana B. Rivadeneira, M. Cecilia Caino, Jae Ho Seo, Alessia Angelin, Wallace C. Douglas, Lucia R. Languino, Dario C. Altieri. Mitochondrial respiration controlled by survivin directs mitochondrial dynamics and tumor cell invasion. [abstract]. In: Proceedings of the AACR Special Conference: Metabolism and Cancer; Jun 7-10, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(1_Suppl):Abstract nr B09. |
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ISSN: | 1541-7786 1557-3125 |
DOI: | 10.1158/1557-3125.METCA15-B09 |