4.5 Article

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

Journal

SCIENCE SIGNALING
Volume 8, Issue 389, Pages -

Publisher

AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scisignal.aab1624

Keywords

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Funding

  1. NIH [P01 CA140043, R01 CA78810, CA190027, R01 CA089720, F32 CA177018]
  2. Office of the Assistant Secretary of Defense for Health Affairs through the Prostate Cancer Research Program [W81XWH-13-1-0193]
  3. Cancer Center Support Grant [CA010815]

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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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