DNA damage triggers squamous metaplasia in human lung and mammary cells via mitotic checkpoints.
Journal
Cell death discovery
ISSN: 2058-7716
Titre abrégé: Cell Death Discov
Pays: United States
ID NLM: 101665035
Informations de publication
Date de publication:
21 Jan 2023
21 Jan 2023
Historique:
received:
10
11
2022
accepted:
11
01
2023
revised:
09
01
2023
entrez:
21
1
2023
pubmed:
22
1
2023
medline:
22
1
2023
Statut:
epublish
Résumé
Epithelial transdifferentiation is frequent in tissue hyperplasia and contributes to disease in various degrees. Squamous metaplasia (SQM) precedes epidermoid lung cancer, an aggressive and frequent malignancy, but it is rare in the epithelium of the mammary gland. The mechanisms leading to SQM in the lung have been very poorly investigated. We have studied this issue on human freshly isolated cells and organoids. Here we show that human lung or mammary cells strikingly undergo SQM with polyploidisation when they are exposed to genotoxic or mitotic drugs, such as Doxorubicin or the cigarette carcinogen DMBA, Nocodazole, Taxol or inhibitors of Aurora-B kinase or Polo-like kinase. To note, the epidermoid response was attenuated when DNA repair was enhanced by Enoxacin or when mitotic checkpoints where abrogated by inhibition of Chk1 and Chk2. The results show that DNA damage has the potential to drive SQM via mitotic checkpoints, thus providing novel molecular candidate targets to tackle lung SCC. Our findings might also explain why SCC is frequent in the lung, but not in the mammary gland and why chemotherapy often causes complicating skin toxicity.
Identifiants
pubmed: 36681661
doi: 10.1038/s41420-023-01330-3
pii: 10.1038/s41420-023-01330-3
pmc: PMC9867756
doi:
Types de publication
Journal Article
Langues
eng
Pagination
21Subventions
Organisme : Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)
ID : (ISCIII)-FEDER, PI17/03107
Organisme : Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)
ID : (ISCIII)-FEDER, PI20/00880
Organisme : Ministerie van Onderwijs, Cultuur en Wetenschap (Ministry of Education, Culture and Science, Netherlands)
ID : 024.003.001
Informations de copyright
© 2023. The Author(s).
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