Systemic organ wasting induced by localized expression of the secreted insulin/IGF antagonist ImpL2.
Systemic organ wasting induced by localized expression of the secreted insulin/IGF antagonist ImpL2.
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DOI：
10.1016/j.devcel.2015.02.012
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发表时间：
2015-04-06
影响因子：
11.8
通讯作者：
Perrimon, Norbert
中科院分区：
文献类型：
--
作者：
Kwon, Young;Song, Wei;Droujinine, Ilia A.;Hu, Yanhui;Asara, John M.;Perrimon, Norbert
器官损耗与细胞和组织的营养和代谢活动的变化有关，在饥饿条件下和在包括癌症在内的疾病情况下观察到。我们已经开发了一种成年果蝇器官损耗模型，即肠道干细胞中Yap1致癌基因Yorkie的激活引起的过度增殖导致卵巢、脂肪体和肌肉的损耗。由于过度增殖的肠道分泌的胰岛素/IGF拮抗剂ImpL2的表达增加，这些器官损耗表型与全身胰岛素/IGF信号的减少有关。引人注目的是，随着Yorkie在肠道中的激活，限制性糖酵解酶和胰岛素/IGF通路的中心组分的表达上调，这可能为这种过度增殖组织逃避ImpL2的作用提供了一种机制。总之，我们的研究为果蝇器官损耗表型的潜在机制以及过度增殖的组织如何适应新陈代谢的全球变化提供了见解。
Organ wasting, related to changes in nutrition and metabolic activity of cells and tissues, is observed under conditions of starvation and in the context of diseases, including cancers. We have developed a model for organ wasting in adult Drosophila, whereby overproliferation induced by activation of Yorkie, the Yap1 oncogene ortholog, in intestinal stem cells leads to wasting of the ovary, fat body, and muscle. These organ-wasting phenotypes are associated with a reduction in systemic insulin/IGF signaling due to increased expression of the secreted insulin/IGF antagonist ImpL2 from the overproliferating gut. Strikingly, expression of rate-limiting glycolytic enzymes and central components of the insulin/IGF pathway is upregulated with activation of Yorkie in the gut, which may provide a mechanism for this overproliferating tissue to evade the effect of ImpL2. Altogether, our study provides insights into the mechanisms underlying organ-wasting phenotypes in Drosophila and how overproliferating tissues adapt to global changes in metabolism.
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DOI：
10.1073/pnas.0702726104
发表时间：
2007-05-15
影响因子：
11.1
作者：
Ja, William W.;Carvalho, Gil B.;Benzer, Seymour
通讯作者：
Benzer, Seymour
影响因子：
7.8
作者：
Alic N;Hoddinott MP;Vinti G;Partridge L
通讯作者：
Partridge L
DOI：
10.1007/bf00577830
发表时间：
1974-01-01
影响因子：
--
作者：
GATEFF, E;SCHNEIDERMAN, HA
通讯作者：
SCHNEIDERMAN, HA
DOI：
10.1038/nrd4161
发表时间：
2014-01
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
通讯作者：
--
影响因子：
14.9
作者：
Murali T;Pacifico S;Yu J;Guest S;Roberts GG 3rd;Finley RL Jr
通讯作者：
Finley RL Jr