Journal of hematology & oncology · 2022
Targeting ERRα promotes cytotoxic effects against acute myeloid leukemia through suppressing mitochondrial oxidative phosphorylation.
Письмо в редакциюПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Seo Wonhyoung, Yoo Seungyeul, Zhong Yi, Lee Sang-Hee, Woo Soo-Yeon, Choi Hee-Seon, Won Minho, Roh Taylor, Jeon Sang Min, Kim Kyeong Tae, Silwal Prashanta, Lee Min Joung, Heo Jun Young, Lawlor Nathan, Kim Sup, Lee Dongjun, Kim Jin-Man, Song Ik-Chan, Zhu Jun, Jo Eun-Kyeong
Аннотация
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.