The tumor suppressor gene fat modulates the EGFR-mediated proliferation control in the imaginal tissues of Drosophila melanogaster
The tumor suppressor gene fat modulates the EGFR-mediated proliferation control in the imaginal tissues of Drosophila melanogaster
复制标题
DOI：
10.1016/j.mod.2004.10.007
复制
发表时间：
2005-02-01
影响因子：
2.6
通讯作者：
Cavicchi, S
中科院分区：
文献类型：
--
作者：
Garoia, F;Grifoni, D;Cavicchi, S
参与细胞黏附的分子既可以调节由可溶性因子触发的早期信号转导事件，也可以调节参与细胞周期进程的下游事件。这些信号的正确整合可以实现适当的细胞生长、分化和最终的组织形态形成，但错误的解释会导致肿瘤生长等病理变化。脂肪钙粘附素是果蝇上皮形态发生、增殖控制和上皮平面极化所必需的一种肿瘤抑制蛋白，它的缺失会导致想象组织的增生性生长。虽然一些分子事件已被描述，通过脂肪参与上皮平面极性的建立，但对脂肪介导的细胞增殖控制的潜在机制知之甚少。在这里，我们提供了脂肪与表皮生长因子受体(EGFR)途径在控制发育中的想象上皮细胞增殖方面的特异性合作的证据。在EGFR过度信号传递之后，增生性幼虫和成体脂肪结构确实经历了一种惊人的、协同的放大。我们进一步证明，这种强大的功能相互作用发生在MAPK激活的下游，通过转录调控参与EGFR核信号的基因。考虑到脂肪突变表现为不同的增生性表型，我们建议了一个模型，在该模型中，脂肪与EGFR途径平行地作用于传递不同的细胞通讯信号：此外，它的功能需要在MAPK下游才能正确呈现汇聚到表皮生长因子受体的生长信号。(C)2004爱思唯尔爱尔兰有限公司。保留所有权利。
Molecules involved in cell adhesion can regulate both early signal transduction events, triggered by soluble factors, and downstream events involved in cell cycle progression. Correct integration of these signals allows appropriate cellular growth, differentiation and ultimately tissue morphogenesis, but incorrect interpretation contributes to pathologies such as tumor growth. The Fat cadherin is a tumor suppressor protein required in Drosophila for epithelial morphogenesis, proliferation control and epithelial planar polarization, and its loss results in a hyperplastic growth of imaginal tissues. While several molecular events have been characterized through which fat participates in the establishment of the epithelial planar polarity, little is known about mechanisms underlying fat-mediated control of cell proliferation. Here we provide evidence that fat specifically cooperates with the epidermal growth factor receptor (EGFR) pathway in controlling cell proliferation in developing imaginal epithelia. Hyperplastic larval and adult fat structures indeed undergo an amazing, synergistic enlargement following to EGFR oversignalling. We further show that such a strong functional interaction occurs downstream of MAPK activation through the transcriptional regulation of genes involved in the EGFR nuclear signalling. Considering that fat mutation shows di per se a hyperplastic phenotype, we suggest a model in which fat acts in parallel to EGFR pathway in transducing different cell communication signals: furthermore its function is requested downstream of MAPK for a correct rendering of the growth signals converging to the epidermal growth factor receptor. (C) 2004 Elsevier Ireland Ltd. All rights reserved.