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

Wonhyoung Seo, Seungyeul Yoo, Yi Zhong, Sang Hee Lee, Soo Yeon Woo, Hee Seon Choi, Minho Won, Taylor Roh, Sang Min Jeon, Kyeong Tae Kim, Prashanta Silwal, Min Joung Lee, Jun Young Heo, Nathan Lawlor, Sup Kim, Dongjun Lee, Jin Man Kim, Ik Chan Song, Jun Zhu, Eun Kyeong Jo

Research output: Contribution to journalLetterpeer-review

3 Scopus citations

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.

Original languageEnglish
Article number156
JournalJournal of Hematology and Oncology
Volume15
Issue number1
DOIs
StatePublished - Dec 2022
Externally publishedYes

Keywords

  • AML
  • Apoptosis
  • ERRα
  • Mitochondrial oxidative phosphorylation

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