RNF40 epigenetically modulates glycolysis to support the aggressiveness of basal-like breast cancer.
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
28 09 2023
28 09 2023
Historique:
received:
05
12
2022
accepted:
15
09
2023
revised:
06
09
2023
medline:
2
10
2023
pubmed:
29
9
2023
entrez:
28
9
2023
Statut:
epublish
Résumé
Triple-negative breast cancer (TNBC) is the most difficult breast cancer subtype to treat due to the lack of targeted therapies. Cancer stem cells (CSCs) are strongly enriched in TNBC lesions and are responsible for the rapid development of chemotherapy resistance and metastasis. Ubiquitin-based epigenetic circuits are heavily exploited by CSCs to regulate gene transcription and ultimately sustain their aggressive behavior. Therefore, therapeutic targeting of these ubiquitin-driven dependencies may reprogram the transcription of CSC and render them more sensitive to standard therapies. In this work, we identified the Ring Finger Protein 40 (RNF40) monoubiquitinating histone 2B at lysine 120 (H2Bub1) as an indispensable E3 ligase for sustaining the stem-cell-like features of the growing mammary gland. In addition, we found that the RNF40/H2Bub1-axis promotes the CSC properties and drug-tolerant state by supporting the glycolytic program and promoting pro-tumorigenic YAP1-signaling in TNBC. Collectively, this study unveils a novel tumor-supportive role of RNF40 and underpins its high therapeutic value to combat the malignant behavior of TNBC.
Identifiants
pubmed: 37770435
doi: 10.1038/s41419-023-06157-5
pii: 10.1038/s41419-023-06157-5
pmc: PMC10539310
doi:
Substances chimiques
Histones
0
Ubiquitin-Protein Ligases
EC 2.3.2.27
Ubiquitins
0
RNF40 protein, human
EC 2.3.2.27
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
641Informations de copyright
© 2023. The Author(s).
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