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上皮细胞连接通过指导平面纺锤体取向来维持组织架构。

Epithelial junctions maintain tissue architecture by directing planar spindle orientation.

机构信息

Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, Missouri 64110, USA.

出版信息

Nature. 2013 Aug 15;500(7462):359-62. doi: 10.1038/nature12335. Epub 2013 Jul 21.

Abstract

During epithelial cell proliferation, planar alignment of the mitotic spindle coordinates the local process of symmetric cell cleavage with the global maintenance of polarized tissue architecture. Although the disruption of planar spindle alignment is proposed to cause epithelial to mesenchymal transition and cancer, the in vivo mechanisms regulating mitotic spindle orientation remain elusive. Here we demonstrate that the actomyosin cortex and the junction-localized neoplastic tumour suppressors Scribbled and Discs large 1 have essential roles in planar spindle alignment and thus the control of epithelial integrity in the Drosophila imaginal disc. We show that defective alignment of the mitotic spindle correlates with cell delamination and apoptotic death, and that blocking the death of misaligned cells is sufficient to drive the formation of basally localized tumour-like masses. These findings indicate a key role for junction-mediated spindle alignment in the maintenance of epithelial integrity, and also reveal a previously unknown cell-death-mediated tumour-suppressor function inherent in the polarized architecture of epithelia.

摘要

在上皮细胞增殖过程中,有丝分裂纺锤体的平面排列将对称细胞分裂的局部过程与极化组织架构的全局维持协调起来。尽管有丝分裂纺锤体取向的平面排列被破坏被认为会导致上皮细胞向间充质转化和癌症,但调节有丝分裂纺锤体取向的体内机制仍不清楚。在这里,我们证明肌动球蛋白皮层和位于连接部的肿瘤抑制因子 Scribbled 和 Discs large 1 在平面纺锤体排列以及果蝇胚胎盘上皮完整性的控制中起着重要作用。我们表明,有丝分裂纺锤体的排列缺陷与细胞分层和细胞凋亡死亡相关,并且阻断排列错误的细胞的死亡足以驱动基底定位的肿瘤样肿块的形成。这些发现表明连接介导的纺锤体排列在维持上皮完整性方面起着关键作用,也揭示了上皮极化结构所固有的以前未知的细胞死亡介导的肿瘤抑制功能。

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