Elevated CXorf67 Expression in PFA Ependymomas Suppresses DNA Repair and Sensitizes to PARP Inhibitors

被引：40

作者：

Han, Jichang ^{[1
,2
]}

Yu, Meng ^{[1
,2
]}

Bai, Yiqin ^{[1
]}

Yu, Jianzhong ^{[3
]}

Jin, Fei ^{[1
]}

Li, Chen ^{[4
]}

Zeng, Rong ^{[2
,4
]}

Peng, Jinghong ^{[1
]}

Li, Ao ^{[5
]}

Song, Xiaomin ^{[1
]}

Li, Hao ^{[3
]}

Wu, Dianqing ^{[5
]}

Li, Lin ^{[1
,2
,6
]}

机构：

[1] Chinese Acad Sci, Univ Chinese Acad Sci, State Key Lab Mol Biol, Inst Biochem & Cell Biol,CAS Ctr Excellence Mol C, Shanghai 200031, Peoples R China

[2] ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China

[3] Fudan Univ, Dept Neurosurg, Childrens Hosp, Shanghai 201102, Peoples R China

[4] Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci, Inst Biochem & Cell Biol, CAS Key Lab Syst Biol, Shanghai 200031, Peoples R China

[5] Yale Sch Med, Dept Pharmacol, New Haven, CT 06510 USA

[6] Univ Chinese Acad Sci, Sch Life Sci, Hangzhou Inst Adv Study, Hangzhou 310024, Peoples R China

来源：

CANCER CELL | 2020年 / 38卷 / 06期

基金：

中国国家自然科学基金;

关键词：

HOMOLOGOUS RECOMBINATION; DAMAGE RESPONSE; CHEMOTHERAPY; COMPONENT; TUMORS; BRCA2;

D O I：

10.1016/j.ccell.2020.10.009

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Ependymoma is the third most common pediatric tumor with posterior fossa group A (PFA) being its most aggressive subtype. Ependymomas are generally refractory to chemotherapies and thus lack any effective treatment. Here, we report that elevated expression of CXorf67 (chromosome X open reading frame 67), which frequently occurs in PFA ependymomas, suppresses homologous recombination (HR)-mediated DNA repair. Mechanistically, CXorf67 interacts with PALB2 and inhibits PALB2-BRCA2 interaction, thereby inhibiting HR repair. Concordantly, tumor cells with high CXorf67 expression levels show increased sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors, especially when combined with radiotherapy. Thus, our findings have revealed a role of CXorf67 in HR repair and suggest that combination of PARP inhibitors with radiotherapy could be an effective treatment option for PFA ependymomas.

引用

页码：844 / +

页数：20

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