Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 114, Issue 8, Pages 1117-1127Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI200422222
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Funding
- NCI NIH HHS [R01 CA078810, CA78810, R01 CA090917] Funding Source: Medline
- NHLBI NIH HHS [R37 HL054131, HL54131, R01 HL054131] Funding Source: Medline
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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 on immunocompromised animals, and abolishes tumor cell apoptosis in vivo. Therefore, mitochondrial survivin orchestrates a novel pathway of apoptosis inhibition, which contributes to tumor progression.
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