The EMT transcription factor ZEB1 governs a fitness-promoting but vulnerable DNA replication stress response.
CP: Cancer
DNA damage response
DNA replication stress
MRE11
ZEB1
cancer
cell cycle
chemoresistance
epithelial-to-mesenchymal transition
heterogeneity
plasticity
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
13 12 2022
13 12 2022
Historique:
received:
13
05
2022
revised:
14
10
2022
accepted:
22
11
2022
entrez:
14
12
2022
pubmed:
15
12
2022
medline:
17
12
2022
Statut:
ppublish
Résumé
The DNA damage response (DDR) and epithelial-to-mesenchymal transition (EMT) are two crucial cellular programs in cancer biology. While the DDR orchestrates cell-cycle progression, DNA repair, and cell death, EMT promotes invasiveness, cellular plasticity, and intratumor heterogeneity. Therapeutic targeting of EMT transcription factors, such as ZEB1, remains challenging, but tumor-promoting DDR alterations elicit specific vulnerabilities. Using multi-omics, inhibitors, and high-content microscopy, we discover a chemoresistant ZEB1-high-expressing sub-population (ZEB1
Identifiants
pubmed: 36516781
pii: S2211-1247(22)01711-9
doi: 10.1016/j.celrep.2022.111819
pii:
doi:
Substances chimiques
Transcription Factors
0
Zinc Finger E-box-Binding Homeobox 1
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
111819Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.