Caspase signalling in the absence of apoptosis drives Jnk-dependent invasion
Caspase signalling in the absence of apoptosis drives Jnk-dependent invasion
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DOI：
10.1038/embor.2012.217
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发表时间：
2013-02-01
期刊：
影响因子：
7.7
通讯作者：
Cagan, Ross L.
中科院分区：
文献类型：
--
作者：
Rudrapatna, Vivek A.;Bangi, Erdem;Cagan, Ross L.
肿瘤进化出多种机制来逃避细胞凋亡，然而许多切除的肿瘤显示出显著升高的caspase活性。此外，半胱天冬酶活性与肿瘤侵袭和不良患者预后呈正相关。这些观察结果表明，半胱天冬酶可能在促进肿瘤侵袭和转移中具有功能作用。利用果蝇的侵袭模型，我们表明精确的效应caspase活性驱动细胞侵袭而不启动细胞凋亡。受影响的细胞表达基质金属蛋白酶Mmp1，并通过激活Jnk进行侵袭。我们的研究结果将Jnk和效应caspase信号在侵袭过程中联系起来，并表明在治疗、免疫监视或内在信号引起的凋亡应激下的肿瘤可能沿着转移级联进一步诱导。
Tumours evolve several mechanisms to evade apoptosis, yet many resected carcinomas show significantly elevated caspase activity. Moreover, caspase activity is positively correlated with tumour aggression and adverse patient outcome. These observations indicate that caspases might have a functional role in promoting tumour invasion and metastasis. Using a Drosophila model of invasion, we show that precise effector caspase activity drives cell invasion without initiating apoptosis. Affected cells express the matrix metalloproteinase Mmp1 and invade by activating Jnk. Our results link Jnk and effector caspase signalling during the invasive process and suggest that tumours under apoptotic stresses from treatment, immune surveillance or intrinsic signals might be induced further along the metastatic cascade.