Notch signaling activates Yorkie non-cell autonomously in Drosophila.

Notch signaling activates Yorkie non-cell autonomously in Drosophila.
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DOI:
10.1371/journal.pone.0037615
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Bergmann A
Bergmann A
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Graves HK;Woodfield SE;Yang CC;Halder G;Bergmann A

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在果蝇的成象上皮细胞中,内细胞性肿瘤抑制基因vps25突变的细胞刺激附近的未转化细胞表达果蝇凋亡抑制蛋白-1(DiAP-1),从而自主地对非细胞的凋亡产生抵抗。在这里,我们证明了DIAP-1的非细胞自主诱导是由HIPPO信号的保守下游效应因子York kie介导的。约克病毒的非细胞自主诱导是由于vps25突变细胞发出的Notch信号。此外,在正常细胞中激活的Notch足以在翅膀成像盘中诱导非细胞自主的约克活动。我们的数据确定了一种新的机制,通过Notch非细胞自主地促进细胞存活,以及肿瘤细胞通过其产生支持肿瘤生长的微环境。
In Drosophila imaginal epithelia, cells mutant for the endocytic neoplastic tumor suppressor gene vps25 stimulate nearby untransformed cells to express Drosophila Inhibitor-of-Apoptosis-Protein-1 (DIAP-1), conferring resistance to apoptosis non-cell autonomously. Here, we show that the non-cell autonomous induction of DIAP-1 is mediated by Yorkie, the conserved downstream effector of Hippo signaling. The non-cell autonomous induction of Yorkie is due to Notch signaling from vps25 mutant cells. Moreover, activated Notch in normal cells is sufficient to induce non-cell autonomous Yorkie activity in wing imaginal discs. Our data identify a novel mechanism by which Notch promotes cell survival non-cell autonomously and by which neoplastic tumor cells generate a supportive microenvironment for tumor growth.
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