Targeting ERRα promotes cytotoxic effects against acute myeloid leukemia through suppressing mitochondrial oxidative phosphorylation

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Title
Targeting ERRα promotes cytotoxic effects against acute myeloid leukemia through suppressing mitochondrial oxidative phosphorylation
Author(s)
W Seo; S Yoo; Y Zhong; S H Lee; Y S Woo; H S Choi; Minho Won; T Roh; S M Jeon; K T Kim; P Silwal; M J Lee; J Y Heo; N Lawlor; S Kim; D Lee; J M Kim; I C Song; J Zhu; E K Jo
Bibliographic Citation
Journal of Hematology & Oncology, vol. 15, pp. 156-156
Publication Year
2022
Abstract
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.
Keyword
AMLERRαMitochondrial oxidative phosphorylationApoptosis
ISSN
1756-8722
Publisher
Springer-BMC
DOI
http://dx.doi.org/10.1186/s13045-022-01372-7
Type
Article
Appears in Collections:
Division of Bio Technology Innovation > BioProcess Engineering Center > 1. Journal Articles
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