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© 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

The mechanics of collective migration in epithelial wound healing have been dissected by a number of studies, many of which make use of simplified in vitro models of cultured epithelial monolayers injured by removal of a strip of cells.1,2 Such models make it possible to investigate the dynamics and mechanisms of cell migration in tissue repair in a tractable system, where epithelial migration is isolated from the complex injury response that takes place in vivo. In a recent study, we identified an unexpected role for the tumour suppressor p53 in leader cell specification.4 We found that p53 levels are elevated in leader cells and, remarkably, that induction of p53 was able to instruct leader behaviour.4 Downstream of p53, its target p21 (also known as cyclin-dependent kinase inhibitor 1A, CDKN1A) is also elevated in leader cells, and both p53 and p21 are sufficient and necessary to promote the leader function.4 Mechanistically, we could determine that p21-dependent CDK inhibition and, consequently, cell-cycle delay instruct leader cell specification.4 In fact, an asymmetry in CDK activity levels between leaders and follower is necessary for the initiation of directed migration.4 Accordingly, inhibiting p53 or p21 reduces the speed of migration and epithelial repair, whereas elevating p53 and p21, via irradiation-induced DNA damage, accelerates migration and repair of injured epithelial monolayers.4 The discovery of the role of p53 in leader cell specification moves the question one step further: Consistent with our own observation that leader cells are removed by cell competition on wound closure, some of these studies also reported that the specialised cells acting as leaders are transient, as cells carrying the leader signature are not observed once the wound has been repaired.7,8 The presence of cell-cycle arrested cells at the front of migrating cell populations is not limited to the context of tissue repair.

Details

Title
From guardian to shepherd: The novel role of p53 in collective cell migration and epithelial repair
Author
Pilia, Giulia 1   VIAFID ORCID Logo  ; Piddini, Eugenia 1 

 School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK 
Section
COMMENTARY
Publication year
2022
Publication date
May 2022
Publisher
John Wiley & Sons, Inc.
e-ISSN
20011326
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2760827999
Copyright
© 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.