Targeting FTO Suppresses Cancer Stem Cell Maintenance and Immune Evasion.
Abstrak
Fat mass and obesity-associated protein (FTO), an RNA N6-methyladenosine (m6A) 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.
Penulis (39)
R. Su
Lei Dong
Yangchan Li
Min Gao
Li Han
M. Wunderlich
Xiaolan Deng
Hongzhi Li
Yue Huang
Lei Gao
Chenying Li
Zhicong Zhao
S. Robinson
B. Tan
Y. Qing
Xi Qin
Emily A. Prince
Jun Xie
H. Qin
Wei Li
Chao Shen
Jie Sun
Prakash Kulkarni
Hengyou Weng
Huilin Huang
Zhenhua Chen
Bin Zhang
Xiwei Wu
M. Olsen
M. Müschen
G. Marcucci
R. Salgia
Ling Li
A. Fathi
Zejuan Li
J. Mulloy
M. Wei
D. Horne
Jianjun Chen
Akses Cepat
- Tahun Terbit
- 2020
- Bahasa
- en
- Total Sitasi
- 628×
- Sumber Database
- Semantic Scholar
- DOI
- 10.1016/j.ccell.2020.04.017
- Akses
- Open Access ✓