Department of Cancer Biology and the Cancer Center
Animals; Apoptosis; Caspases; Cell Hypoxia; Cell Line, Tumor; Endopeptidase K; Enzyme Activation; Enzyme Inhibitors; Hela Cells; Humans; In Situ Nick-End Labeling; Microtubule-Associated Proteins; Mitochondria; Neoplasm Proteins; Neoplasms; Recombinant Fusion Proteins; Staurosporine; Subcellular Fractions
Evasion of apoptosis is a hallmark of cancer, but the molecular circuitries of this process are not understood. Here we show that survivin, a member of the inhibitor of apoptosis gene family that is overexpressed in cancer, exists in a novel mitochondrial pool in tumor cells. In response to cell death stimulation, mitochondrial survivin is rapidly discharged in the cytosol, where it prevents caspase activation and inhibits apoptosis. Selective targeting of survivin to mitochondria enhances colony formation in soft agar, accelerates tumor growth in immunocompromised animals, and abolishes tumor cell apoptosis in vivo. Therefore, mitochondrial survivin orchestrates a novel pathway of apoptosis inhibition, which contributes to tumor progression.
DOI of Published Version
J Clin Invest. 2004 Oct;114(8):1117-27. Link to article on publisher's site
The Journal of clinical investigation
Dohi, Takehiko; Beltrami, Elena; Wall, Nathan R.; Plescia, Janet; and Altieri, Dario C., "Mitochondrial survivin inhibits apoptosis and promotes tumorigenesis" (2004). Open Access Articles. 996.