A bacterial protease depletes c-MYC and increases survival in mouse models of bladder and colon cancer.
Journal
Nature biotechnology
ISSN: 1546-1696
Titre abrégé: Nat Biotechnol
Pays: United States
ID NLM: 9604648
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
received:
27
08
2019
accepted:
15
12
2020
pubmed:
13
2
2021
medline:
28
8
2021
entrez:
12
2
2021
Statut:
ppublish
Résumé
Is the oncogene MYC upregulated or hyperactive? In the majority of human cancers, finding agents that target c-MYC has proved difficult. Here we report specific bacterial effector molecules that inhibit cellular MYC (c-MYC) in human cells. We show that uropathogenic Escherichia coli (UPEC) degrade the c-MYC protein and attenuate MYC expression in both human cells and animal tissues. c-MYC protein was rapidly degraded by both cell-free bacterial lysates and the purified bacterial protease Lon. In mice, intravesical or peroral delivery of Lon protease delayed tumor progression and increased survival in MYC-dependent bladder and colon cancer models, respectively. These results suggest that bacteria have evolved strategies to control c-MYC tissue levels in the host and that the Lon protease shows promise for therapeutic targeting of c-MYC in cancer.
Identifiants
pubmed: 33574609
doi: 10.1038/s41587-020-00805-3
pii: 10.1038/s41587-020-00805-3
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
754-764Commentaires et corrections
Type : CommentIn
Type : CommentIn
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