KMT2A associates with PHF5A-PHF14-HMG20A-RAI1 subcomplex in pancreatic cancer stem cells and epigenetically regulates their characteristics.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
14 09 2023
14 09 2023
Historique:
received:
14
11
2022
accepted:
30
08
2023
medline:
18
9
2023
pubmed:
15
9
2023
entrez:
14
9
2023
Statut:
epublish
Résumé
Pancreatic cancer (PC), one of the most aggressive and life-threatening human malignancies, is known for its resistance to cytotoxic therapies. This is increasingly ascribed to the subpopulation of undifferentiated cells, known as pancreatic cancer stem cells (PCSCs), which display greater evolutionary fitness than other tumor cells to evade the cytotoxic effects of chemotherapy. PCSCs are crucial for tumor relapse as they possess 'stem cell-like' features that are characterized by self-renewal and differentiation. However, the molecular mechanisms that maintain the unique characteristics of PCSCs are poorly understood. Here, we identify the histone methyltransferase KMT2A as a physical binding partner of an RNA polymerase-associated PHF5A-PHF14-HMG20A-RAI1 protein subcomplex and an epigenetic regulator of PCSC properties and functions. Targeting the protein subcomplex in PCSCs with a KMT2A-WDR5 inhibitor attenuates their self-renewal capacity, cell viability, and in vivo tumorigenicity.
Identifiants
pubmed: 37709746
doi: 10.1038/s41467-023-41297-4
pii: 10.1038/s41467-023-41297-4
pmc: PMC10502114
doi:
Substances chimiques
Histone Methyltransferases
EC 2.1.1.-
HMG20A protein, human
0
High Mobility Group Proteins
0
PHF5A protein, human
0
Trans-Activators
0
RNA-Binding Proteins
0
WDR5 protein, human
0
Intracellular Signaling Peptides and Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5685Informations de copyright
© 2023. Springer Nature Limited.
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