Targeting ERRα promotes cytotoxic effects against acute myeloid leukemia through suppressing mitochondrial oxidative phosphorylation.
AML
Apoptosis
ERRα
Mitochondrial oxidative phosphorylation
Journal
Journal of hematology & oncology
ISSN: 1756-8722
Titre abrégé: J Hematol Oncol
Pays: England
ID NLM: 101468937
Informations de publication
Date de publication:
26 10 2022
26 10 2022
Historique:
received:
11
07
2022
accepted:
13
10
2022
entrez:
27
10
2022
pubmed:
28
10
2022
medline:
29
10
2022
Statut:
epublish
Résumé
Acute myeloid leukemia (AML) is an aggressive blood cancer with poor clinical outcomes. Emerging data suggest that mitochondrial oxidative phosphorylation (mtOXPHOS) plays a significant role in AML tumorigenesis, progression, and resistance to chemotherapies. However, how the mtOXPHOS is regulated in AML cells is not well understood. In this study, we investigated the oncogenic functions of ERRα in AML by combining in silico, in vitro, and in vivo analyses and showed ERRα is a key regulator of mtOXPHOS in AML cells. The increased ERRα level was associated with worse clinical outcomes of AML patients. Single cell RNA-Seq analysis of human primary AML cells indicated that ERRα-expressing cancer cells had significantly higher mtOXPHOS enrichment scores. Blockade of ERRα by pharmacologic inhibitor (XCT-790) or gene silencing suppressed mtOXPHOS and increased anti-leukemic effects in vitro and in xenograft mouse models.
Identifiants
pubmed: 36289517
doi: 10.1186/s13045-022-01372-7
pii: 10.1186/s13045-022-01372-7
pmc: PMC9597966
doi:
Substances chimiques
Antineoplastic Agents
0
Types de publication
Letter
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
156Subventions
Organisme : Korea Health Industry Development Institute
ID : HR20C0025
Organisme : Korea Basic Science Institute
ID : C140440
Organisme : National Research Foundation of Korea
ID : 2017R1A5A2015385
Informations de copyright
© 2022. The Author(s).
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