Research ArticleCancer

Survivin promotes oxidative phosphorylation, subcellular mitochondrial repositioning, and tumor cell invasion

Sci. Signal.  11 Aug 2015:
Vol. 8, Issue 389, pp. ra80
DOI: 10.1126/scisignal.aab1624

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Energy for metastasis

Survivin is a member of a family of proteins that inhibit cell death, and a drug that inhibits this protein is undergoing clinical testing. Survivin is found both in the cytoplasm and in mitochondria, the organelles that produce ATP (adenosine 5′-triphosphate). Rivadeneira et al. found that in PC3 prostate cancer cells, the mitochondrial pool of survivin enhanced metabolic processes that produce ATP and promoted the relocalization of mitochondria to the areas of the cell that would need energy to fuel the subcellular changes that are required for migration. Targeting survivin, either pharmacologically or with RNA interference, decreased the movement of PC3 cells. Overexpressing mitochondrial survivin in cancer cells that have low motility increased their ability to metastasize in mice.

Abstract

Survivin promotes cell division and suppresses apoptosis in many human cancers, and increased abundance correlates with metastasis and poor prognosis. We showed that a pool of survivin that localized to the mitochondria of certain tumor cell lines enhanced the stability of oxidative phosphorylation complex II, which promoted cellular respiration. Survivin also supported the subcellular trafficking of mitochondria to the cortical cytoskeleton of tumor cells, which was associated with increased membrane ruffling, increased focal adhesion complex turnover, and increased tumor cell migration and invasion in cultured cells, and enhanced metastatic dissemination in vivo. Therefore, we found that mitochondrial respiration enhanced by survivin contributes to cancer metabolism, and relocalized mitochondria may provide a “regional” energy source to fuel tumor cell invasion and metastasis.

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