Mitochondrial survivin inhibits apoptosis and promotes tumorigenesis

Takehiko Dohi, Elena Beltrami, Nathan R. Wall, Janet Plescia, Dario C. Altieri

Research output: Contribution to journalArticle

310 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1117-1127
Number of pages11
JournalJournal of Clinical Investigation
Volume114
Issue number8
DOIs
StatePublished - Oct 1 2004

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Carcinogenesis
Apoptosis
Neoplasms
Caspases
Cytosol
Agar
Mitochondria
Cell Death
Growth
Genes

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Dohi, Takehiko ; Beltrami, Elena ; Wall, Nathan R. ; Plescia, Janet ; Altieri, Dario C. / Mitochondrial survivin inhibits apoptosis and promotes tumorigenesis. In: Journal of Clinical Investigation. 2004 ; Vol. 114, No. 8. pp. 1117-1127.
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Mitochondrial survivin inhibits apoptosis and promotes tumorigenesis. / Dohi, Takehiko; Beltrami, Elena; Wall, Nathan R.; Plescia, Janet; Altieri, Dario C.

In: Journal of Clinical Investigation, Vol. 114, No. 8, 01.10.2004, p. 1117-1127.

Research output: Contribution to journalArticle

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