The tumor suppressor CYLD controls epithelial morphogenesis and homeostasis by regulating mitotic spindle behavior and adherens junction assembly
The tumor suppressor CYLD controls epithelial morphogenesis and homeostasis by regulating mitotic spindle behavior and adherens junction assembly
复制标题
肿瘤抑制因子 CYLD 通过调节有丝分裂纺锤体行为和粘附连接组装来控制上皮形态发生和稳态
DOI：
10.1016/j.jgg.2017.06.002
复制
发表时间：
2017-07-20
影响因子：
5.9
通讯作者：
Zhou, Jun
中科院分区：
文献类型：
--
作者：
Xie, Wei;Yang, Yunfan;Zhou, Jun
Epithelial morphogenesis and homeostasis are essential for animal development and tissue regeneration, and epithelial disorganization is associated with developmental disorders and tumorigenesis. However, the molecular mechanisms that contribute to the morphogenesis and homeostasis of the epithelium remain elusive. Herein, we report a novel role for the cylindromatosis (CYLD) tumor suppressor in these events. Our results show that CYLD depletion disrupts epithelial organization in both Drosophila egg chambers and mouse skin and intestinal epithelia. Microscopic analysis of proliferating cells in mouse epithelial tissues and cultured organoids reveals that loss of CYLD synergizes with tumor-promoting agents to cause the misorientation of the mitotic spindle. Mechanistic studies show that CYLD accumulates at the cell cortex in epithelial tissues and cultured cells, where it promotes the formation of epithelial adherens junctions through the modulation of microtubule dynamics. These data suggest that CYLD controls epithelial morphogenesis and homeostasis by modulating the assembly of adherens junctions and ensuring proper orientation of the mitotic spindle. Our findings thus provide novel insight into the role of CYLD in development, tissue homeostasis, and tumorigenesis. Copyright (C) 2017, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Limited and Science Press. All rights reserved.
