Abstract

To explain the excess cancer rate in males, several candidates for “escape from X-inactivation tumor-suppressor” (EXITS) were recently identified. In this report we provide direct experimental evidence supporting UTX’s role as an EXITS gene. Using a mouse lymphoma model, we show clear dosage effect of UTX copy number during tumorigenesis, which strongly supports the EXITS theory. Importantly, UTX deletion not only accelerates lymphomagenesis, it also strongly promotes tumor progression. UTX-knockout tumors are more aggressive, showing enhanced brain dissemination and formation of blood vessels. Efnb1 is overexpressed in UTX KO tumors and can lead to such phenotypes. In human patients, lymphomas with low UTX expression also express high levels of Efnb1, and cause significantly poor survival. Lastly, we show that UTX deficiency renders lymphoma sensitive to cytarabine treatment. Taken together, these data highlight UTX loss’s profound impacts on tumor initiation and drug response.

Details

Title
UTX is an escape from X-inactivation tumor-suppressor in B cell lymphoma
Author
Li, Xiaoxi 1   VIAFID ORCID Logo  ; Zhang, Yanli 2 ; Zheng, Liting 3 ; Liu, Mingxian 2 ; Chen, Charlie Degui 3 ; Jiang, Hai 2   VIAFID ORCID Logo 

1  State Key Laboratory of Cell Biology, Key Laboratory of Systems Biology, Innovation Center for Cell Signaling Network, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China; Jiangsu Key Laboratory of Medical Science and Laboratory Medicine. School of Medicine, Jiangsu University, Jiangsu, China 
2  State Key Laboratory of Cell Biology, Key Laboratory of Systems Biology, Innovation Center for Cell Signaling Network, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China 
3  State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, Innovation Center for Cell Signaling Network, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China 
Pages
1-10
Publication year
2018
Publication date
Jul 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-018-05084-w
ProQuest document ID
2069382534
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.