Survivin promotes oxidative phosphorylation, subcellular mitochondrial repositioning, and tumor cell invasion.
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.
Prostate Cancer Discovery and Development Program, The Wistar Institute, Philadelphia, PA 19104, USA. Tumor Microenvironment and Metastasis Program, The Wistar Institute, Philadelphia, PA 19104, USA.
Dayana B
DB
Rivadeneira
Prostate Cancer Discovery and Development Program, The Wistar Institute, Philadelphia, PA 19104, USA. Tumor Microenvironment and Metastasis Program, The Wistar Institute, Philadelphia, PA 19104, USA.
M Cecilia
MC
Caino
Prostate Cancer Discovery and Development Program, The Wistar Institute, Philadelphia, PA 19104, USA. Tumor Microenvironment and Metastasis Program, The Wistar Institute, Philadelphia, PA 19104, USA.
Jae Ho
JH
Seo
Center for Mitochondrial and Epigenomic Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Alessia
A
Angelin
Center for Mitochondrial and Epigenomic Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Douglas C
DC
Wallace
Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Lucia R
LR
Languino
Prostate Cancer Discovery and Development Program, The Wistar Institute, Philadelphia, PA 19104, USA. Tumor Microenvironment and Metastasis Program, The Wistar Institute, Philadelphia, PA 19104, USA. daltieri@wistar.org.
Dario C
DC
Altieri
D002465:Cell Movement; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism*; D061986:MCF-7 Cells; D008297:Male; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010085:Oxidative Phosphorylation; D010101:Oxygen Consumption; D000077022:Survivin
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins; D000077022:Survivin