Type I IFNs promote cancer cell stemness by triggering the epigenetic regulator KDM1B.
Journal
Nature immunology
ISSN: 1529-2916
Titre abrégé: Nat Immunol
Pays: United States
ID NLM: 100941354
Informations de publication
Date de publication:
09 2022
09 2022
Historique:
received:
18
04
2021
accepted:
17
07
2022
pubmed:
25
8
2022
medline:
20
9
2022
entrez:
24
8
2022
Statut:
ppublish
Résumé
Cancer stem cells (CSCs) are a subpopulation of cancer cells endowed with high tumorigenic, chemoresistant and metastatic potential. Nongenetic mechanisms of acquired resistance are increasingly being discovered, but molecular insights into the evolutionary process of CSCs are limited. Here, we show that type I interferons (IFNs-I) function as molecular hubs of resistance during immunogenic chemotherapy, triggering the epigenetic regulator demethylase 1B (KDM1B) to promote an adaptive, yet reversible, transcriptional rewiring of cancer cells towards stemness and immune escape. Accordingly, KDM1B inhibition prevents the appearance of IFN-I-induced CSCs, both in vitro and in vivo. Notably, IFN-I-induced CSCs are heterogeneous in terms of multidrug resistance, plasticity, invasiveness and immunogenicity. Moreover, in breast cancer (BC) patients receiving anthracycline-based chemotherapy, KDM1B positively correlated with CSC signatures. Our study identifies an IFN-I → KDM1B axis as a potent engine of cancer cell reprogramming, supporting KDM1B targeting as an attractive adjunctive to immunogenic drugs to prevent CSC expansion and increase the long-term benefit of therapy.
Identifiants
pubmed: 36002648
doi: 10.1038/s41590-022-01290-3
pii: 10.1038/s41590-022-01290-3
pmc: PMC9477743
doi:
Substances chimiques
Anthracyclines
0
Interferon Type I
0
Histone Demethylases
EC 1.14.11.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1379-1392Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
© 2022. The Author(s).
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