UTX is an escape from X-inactivation tumor-suppressor in B cell lymphoma

Nature Communications
Xiaoxi LiHai Jiang

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.

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Citations

Jan 11, 2019·International Journal of Cancer. Journal International Du Cancer·Wolfgang A SchulzAnnemarie Greife
Feb 11, 2020·Cellular and Molecular Life Sciences : CMLS·Dan WangCan Guo
May 3, 2019·Signal Transduction and Targeted Therapy·Hai Jiang
Apr 17, 2020·Biology of Sex Differences·Joshua B RubinJingqin Luo
Feb 6, 2020·International Journal of Molecular Sciences·Eleonora VecchioIleana Quinto
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Apr 26, 2020·Signal Transduction and Targeted Therapy·Hai Jiang
May 1, 2021·Biochemical Society Transactions·Christine R Keenan
Aug 21, 2020·Molecular and Cellular Biology·Nhien TranKai Ge

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Datasets Mentioned

BETA
GSE10846
18
SRP135245

Methods Mentioned

BETA
FACS
dissection

Software Mentioned

Siscales
NOISeq
SurvExpress

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