Mitochondrial survivin inhibits apoptosis and promotes tumorigenesis
Mitochondrial survivin inhibits apoptosis and promotes tumorigenesis
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DOI：
10.1172/jci200422222
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发表时间：
2004-10-01
影响因子：
15.9
通讯作者：
Altieri, DC
中科院分区：
文献类型：
--
作者：
Dohi, T;Beltrami, E;Altieri, DC
逃避细胞凋亡是癌症的一个标志，但这一过程的分子电路尚不清楚。在这里，我们表明，生存素，在癌症中过表达的凋亡抑制基因家族的成员，存在于一个新的肿瘤细胞线粒体池。响应于细胞死亡刺激，线粒体存活素在胞质溶胶中快速排出，在胞质溶胶中其阻止半胱天冬酶活化并抑制细胞凋亡。生存素选择性靶向线粒体增强软琼脂集落形成，加速免疫功能低下动物的肿瘤生长，并废除体内肿瘤细胞凋亡。因此，线粒体生存素协调了一种新的凋亡抑制途径，这有助于肿瘤的进展。
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.