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靶向FTO可抑制肿瘤干细胞的维持和免疫逃避
作者:小柯机器人 发布时间:2020/6/12 22:06:56

美国贝克曼研究所Jianjun Chen小组的一项最新研究发现,靶向脂肪和肥胖相关蛋白(FTO)可以抑制癌症干细胞的维持和免疫逃逸。这一研究成果在线发表在2020年6月11日出的《癌细胞》上。

研究人员发现了两种有效的小分子FTO抑制剂,它们在多种类型的癌症中均表现出强大的抗肿瘤活性。研究显示,敲除FTO或药物抑制可通过抑制免疫检查点基因(尤其是LILRB4)的表达显著减弱白血病干细胞/启动细胞的自我更新并重编程免疫应答。

抑制FTO使白血病细胞对T细胞的细胞毒性敏感,并克服了低甲基化剂诱导的免疫逃逸。这项研究揭示了FTO在癌症干细胞的自我更新和免疫逃逸中的关键作用,并突出了针对FTO进行癌症治疗的广泛应用潜力。

据了解,FTO,一种RNA N6-甲基腺苷(m6A)脱甲基酶,在各种癌症中发挥致癌作用,这为开发有效的靶向治疗药物提供了潜在靶点。

附:英文原文

Title: Targeting FTO Suppresses Cancer Stem Cell Maintenance and Immune Evasion

Author: Rui Su, Lei Dong, Yangchan Li, Min Gao, Li Han, Mark Wunderlich, Xiaolan Deng, Hongzhi Li, Yue Huang, Lei Gao, Chenying Li, Zhicong Zhao, Sean Robinson, Brandon Tan, Ying Qing, Xi Qin, Emily Prince, Jun Xie, Hanjun Qin, Wei Li, Chao Shen, Jie Sun, Prakash Kulkarni, Hengyou Weng, Huilin Huang, Zhenhua Chen, Bin Zhang, Xiwei Wu, Mark J. Olsen, Markus Müschen, Guido Marcucci, Ravi Salgia, Ling Li, Amir T. Fathi, Zejuan Li, James C. Mulloy, Minjie Wei, David Horne, Jianjun Chen

Issue&Volume: 2020-06-11

Abstract: Fat mass and obesity-associated protein (FTO), an RNA N6-methyladenosine (m6A) demethylase, plays oncogenic roles in various cancers, presenting an opportunityfor the development of effective targeted therapeutics. Here, we report two potentsmall-molecule FTO inhibitors that exhibit strong anti-tumor effects in multiple typesof cancers. We show that genetic depletion and pharmacological inhibition of FTO dramaticallyattenuate leukemia stem/initiating cell self-renewal and reprogram immune responseby suppressing expression of immune checkpoint genes, especially LILRB4. FTO inhibition sensitizes leukemia cells to T cell cytotoxicity and overcomes hypomethylatingagent-induced immune evasion. Our study demonstrates that FTO plays critical rolesin cancer stem cell self-renewal and immune evasion and highlights the broad potentialof targeting FTO for cancer therapy.

DOI: 10.1016/j.ccell.2020.04.017

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(20)30216-6

期刊信息

Cancer Cell:《癌细胞》,创刊于2002年。隶属于细胞出版社,最新IF:23.916
官方网址:https://www.cell.com/cancer-cell/home
投稿链接:https://www.editorialmanager.com/cancer-cell/default.aspx