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

Autor: 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
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Journal of Hematology & Oncology, Vol 15, Iss 1, Pp 1-6 (2022)
Druh dokumentu: article
ISSN: 1756-8722
DOI: 10.1186/s13045-022-01372-7
Popis: 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.
Databáze: Directory of Open Access Journals
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