Graves Hillary K, Woodfield Sarah E, Yang Chih-Chao, Halder Georg, Bergmann Andreas
Department of Biochemistry and Molecular Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
PLoS One. 2012;7(6):e37615. doi: 10.1371/journal.pone.0037615. Epub 2012 Jun 5.
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.
在果蝇成虫上皮细胞中，内吞性肿瘤抑制基因vps25发生突变的细胞会刺激附近未转化的细胞表达果蝇凋亡抑制蛋白1（DIAP - 1），从而非细胞自主性地赋予细胞对凋亡的抗性。在此，我们表明DIAP - 1的非细胞自主性诱导是由Hippo信号通路中保守的下游效应因子Yorkie介导的。Yorkie的非细胞自主性诱导是由于vps25突变细胞发出的Notch信号。此外，正常细胞中激活的Notch足以在翅成虫盘中诱导非细胞自主性的Yorkie活性。我们的数据确定了一种新机制，通过该机制Notch非细胞自主性地促进细胞存活，并且肿瘤细胞借此为肿瘤生长生成支持性微环境。
