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Targeting FTO Suppresses Cancer Stem Cell Maintenance and Immune Evasion

文献类型：期刊论文

作者Su, Rui2; Dong, Lei2; Li, Yangchan1,2; Gao, Min2,12,13; Han, Li2,3; Wunderlich, Mark4; Deng, Xiaolan2; Li, Hongzhi5; Huang, Yue7; Gao, Lei2,14
刊名CANCER CELL
出版日期2020-07-13
卷号38期号:1页码:79-+
ISSN号1535-6108
DOI10.1016/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.
WOS关键词OBESITY-ASSOCIATED PROTEIN ; PHASE-I ; MYELOID-LEUKEMIA ; FAT MASS ; RNA DEMETHYLASE ; BISANTRENE ; DRUG ; EXPRESSION ; NSC-368390 ; PROMOTES
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研究方向Oncology ; Cell Biology
语种英语
WOS记录号WOS:000550244200014
出版者CELL PRESS
源URL[http://119.78.100.183/handle/2S10ELR8/292150]  
专题新药研究国家重点实验室
通讯作者Chen, Jianjun
作者单位1.Sun Yat Sen Univ, Affiliated Hosp 1, Dept Radiat Oncol, Guangzhou 510080, Guangdong, Peoples R China
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-+.

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来源：上海药物研究所

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