Competition for Space Induces Cell Elimination through Compaction-Driven ERK Downregulation.
Drosophila
EGFR
ERK
Hid
apoptosis
cell competition
epithelium
mechanotransduction
Journal
Current biology : CB
ISSN: 1879-0445
Titre abrégé: Curr Biol
Pays: England
ID NLM: 9107782
Informations de publication
Date de publication:
07 01 2019
07 01 2019
Historique:
received:
25
07
2018
revised:
01
10
2018
accepted:
01
11
2018
pubmed:
18
12
2018
medline:
24
1
2020
entrez:
18
12
2018
Statut:
ppublish
Résumé
The plasticity of developing tissues relies on the adjustment of cell survival and growth rate to environmental cues. This includes the effect of mechanical cues on cell survival. Accordingly, compaction of an epithelium can lead to cell extrusion and cell death. This process was proposed to contribute to tissue homeostasis but also to facilitate the expansion of pretumoral cells through the compaction and elimination of the neighboring healthy cells. However, we know very little about the pathways that can trigger apoptosis upon tissue deformation, and the contribution of compaction-driven death to clone expansion has never been assessed in vivo. Using the Drosophila pupal notum and a new live sensor of ERK, we show first that tissue compaction induces cell elimination through the downregulation of epidermal growth factor receptor/extracellular signal regulated kinase (EGFR/ERK) pathway and the upregulation of the pro-apoptotic protein Hid. Those results suggest that the sensitivity of EGFR/ERK pathway to mechanics could play a more general role in the fine tuning of cell elimination during morphogenesis and tissue homeostasis. Second, we assessed in vivo the contribution of compaction-driven death to pretumoral cell expansion. We found that the activation of the oncogene Ras in clones can downregulate ERK and activate apoptosis in the neighboring cells through their compaction, which eventually contributes to Ras clone expansion. The mechanical modulation of EGFR/ERK during growth-mediated competition for space may contribute to tumor progression.
Identifiants
pubmed: 30554899
pii: S0960-9822(18)31473-8
doi: 10.1016/j.cub.2018.11.007
pmc: PMC6331351
pii:
doi:
Substances chimiques
Drosophila Proteins
0
ErbB Receptors
EC 2.7.10.1
Extracellular Signal-Regulated MAP Kinases
EC 2.7.11.24
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
23-34.e8Informations de copyright
Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.
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