The tumor suppressor CYLD controls epithelial morphogenesis and homeostasis by regulating mitotic spindle behavior and adherens junction assembly

Wei Xie^{a, #},
Yunfan Yang^{b, #},
Siqi Gao^b,
Ting Song^a,
Yuhan Wu^a,
Dengwen Li^b,
Min Liu^a,
Jun Zhou^{a, b
, ,}

a.
Key Laboratory of Animal Resistance Biology of Shandong Province, Institute of Biomedical Sciences, College of Life Sciences, Shandong Normal University, Jinan 250014, China
b.
State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China

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Corresponding author: E-mail address: junzhou@sdnu.edu.cn (Jun Zhou)

These authors contributed equally to this work.

摘要

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Abstract: 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.
- Epithelium /
- CYLD /
- Mitotic spindle /
- Cell cortex /
- Adherens junction
These authors contributed equally to this work.
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参考文献(48)

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