p53 directs leader cell behavior, migration, and clearance during epithelial repair

被引：41

作者：

Kozyrska, Kasia ^{[1
,2
,3
,4
]}

Pilia, Giulia ^{[1
]}

Vishwakarma, Medhavi ^{[1
,5
]}

Wagstaff, Laura ^{[2
,3
,6
]}

Goschorska, Maja ^{[1
]}

Cirillo, Silvia ^{[1
]}

Mohamad, Saad ^{[1
]}

Gallacher, Kelli ^{[1
,7
]}

Salas, Rafael E. Carazo ^{[1
]}

Piddini, Eugenia ^{[1
]}

机构：

[1] Univ Bristol, Sch Cellular & Mol Med, Bristol BS8 1TD, Avon, England

[2] Univ Cambridge, Wellcome Trust Canc Res UK Gurdon Inst, Cambridge CB2 1QN, England

[3] Univ Cambridge, Dept Zool, Cambridge CB2 1QN, England

[4] Horizon Discovery Ltd, Cambridge CB25 9TL, England

[5] Indian Inst Sci, Ctr BioSyst Sci & Engn, Bangalore 560012, Karnataka, India

[6] Univ East Anglia, Sch Biol Sci, Norwich NR4 7UA, Norfolk, England

[7] Univ Bath, Dept Biol & Biochem, Bath BA2 7AY, Avon, England

来源：

SCIENCE | 2022年 / 375卷 / 6581期

基金：

英国惠康基金;

关键词：

MITOMYCIN C; REGENERATION; INHIBITION; ACTIVATION; SENESCENCE; DYNAMICS; KINASE; FRONT; MODEL;

D O I：

10.1126/science.abl8876

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Epithelial cells migrate across wounds to repair injured tissue. Leader cells at the front of migrating sheets often drive this process. However, it is unclear how leaders emerge from an apparently homogeneous epithelial cell population. We characterized leaders emerging from epithelial monolayers in cell culture and found that they activated the stress sensor p53, which was sufficient to initiate leader cell behavior. p53 activated the cell cycle inhibitor p21WAF1/CIP1, which in turn induced leader behavior through inhibition of cyclin-dependent kinase activity. p53 also induced crowding hypersensitivity in leader cells such that, upon epithelial closure, they were eliminated by cell competition. Thus, mechanically induced p53 directs emergence of a transient population of leader cells that drive migration and ensures their clearance upon epithelial repair. © 2022 American Association for the Advancement of Science. All rights reserved.

引用

页码：628 / +

页数：23

共 38 条

[1] Tetraploid state induces p53-dependent arrest of nontransformed mammalian cells in G1 [J].