Targeting FTO Suppresses Cancer Stem Cell Maintenance and Immune Evasion

doi:10.1016/j.ccell.2020.04.017

	Targeting FTO Suppresses Cancer Stem Cell Maintenance and Immune Evasion
	Su, Rui 2; Dong, Lei 2; Li, Yangchan 2,11; Gao, Min 2,12,13; Han, Li 2,3; Wunderlich, Mark 4; Deng, Xiaolan 2; Li, Hongzhi 5; Huang, Yue 7; Gao, Lei 2,14
刊名	CANCER CELL
	2020-07-13
卷号	38 期号:1 页码:79-+
ISSN号	1535-6108
DOI	10.1016/j.ccell.2020.04.017
通讯作者	Chen, Jianjun(jianchen@coh.org)
英文摘要	Fat mass and obesity-associated protein (FTO), an RNA N-6-methyladenosine (m(6)A) demethylase, plays oncogenic roles in various cancers, presenting an opportunity for the development of effective targeted therapeutics. Here, we report two potent small-molecule FTO inhibitors that exhibit strong anti-tumor effects in multiple types of cancers. We show that genetic depletion and pharmacological inhibition of FTO dramatically attenuate leukemia stem/initiating cell self-renewal and reprogram immune response by suppressing expression of immune checkpoint genes, especially LILRB4. FTO inhibition sensitizes leukemia cells to T cell cytotoxicity and overcomes hypomethylating agent-induced immune evasion. Our study demonstrates that FTO plays critical roles in cancer stem cell self-renewal and immune evasion and highlights the broad potential of targeting FTO for cancer therapy.
资助项目	Hematopoietic Tissue Biorepository core at City of Hope Comprehensive Cancer Center - National Cancer Institute of the US National Institutes of Health (NIH)[P30CA33572] ; NIH[R01 CA243386] ; NIH[R01 CA214965] ; NIH[R01 CA236399] ; NIH[R01 CA211614] ; NIH[R01 DK124116] ; NIH[R50CA211404] ; NIH[R35CA197628] ; NIH[U10CA180827] ; NIH[R01CA137060] ; NIH[R01CA157644] ; NIH[R01CA172558] ; NIH[R01CA213138] ; The Margaret Early Medical Research Trust ; American Cancer Society Research Scholar grant
WOS关键词	OBESITY-ASSOCIATED PROTEIN ; PHASE-I ; MYELOID-LEUKEMIA ; FAT MASS ; RNA DEMETHYLASE ; BISANTRENE ; DRUG ; EXPRESSION ; NSC-368390 ; PROMOTES
WOS研究方向	Oncology ; Cell Biology
语种	英语
出版者	CELL PRESS
WOS记录号	WOS:000550244200014
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/292150]
专题	中国科学院上海药物研究所
通讯作者	Chen, Jianjun
作者单位	1.City Hope Natl Med Ctr, Gehr Family Ctr Leukemia Res, Duarte, CA 91010 USA 2.Beckman Res Inst City Hope, Dept Syst Biol, Monrovia, CA 91016 USA 3.China Med Univ, Sch Pharm, Shenyang 110001, Liaoning, Peoples R China 4.Cincinnati Childrens Hosp Med Ctr, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA 5.Beckman Res Inst City Hope, Dept Mol Med, Duarte, CA 91010 USA 6.City Hope Med Ctr, Beckman Res Inst, Integrat Genom Core, Duarte, CA 91010 USA 7.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 8.Beckman Res Inst City Hope, Dept Hematol Malignancies Translat Sci, Monrovia, CA 91016 USA 9.City Hope Natl Med Ctr, Dept Med Oncol & Therapeut Res, Duarte, CA 91010 USA 10.City Hope Natl Med Ctr, City Hope Comprehens Canc Ctr, Duarte, CA 91010 USA
推荐引用方式 GB/T 7714	Su, Rui,Dong, Lei,Li, Yangchan,et al. Targeting FTO Suppresses Cancer Stem Cell Maintenance and Immune Evasion[J]. CANCER CELL,2020,38(1):79-+.
APA	Su, Rui.,Dong, Lei.,Li, Yangchan.,Gao, Min.,Han, Li.,...&Chen, Jianjun.(2020).Targeting FTO Suppresses Cancer Stem Cell Maintenance and Immune Evasion.CANCER CELL,38(1),79-+.
MLA	Su, Rui,et al."Targeting FTO Suppresses Cancer Stem Cell Maintenance and Immune Evasion".CANCER CELL 38.1(2020):79-+.