2. Academic Validation
  3. Elevated CXorf67 Expression in PFA Ependymomas Suppresses DNA Repair and Sensitizes to PARP Inhibitors

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

  • Cancer Cell. 2020 Dec 14;38(6):844-856.e7. doi: 10.1016/j.ccell.2020.10.009.
Jichang Han 1,  Meng Yu 1,  Yiqin Bai 2,  Jianzhong Yu 3,  Fei Jin 2,  Chen Li 4,  Rong Zeng 5,  Jinghong Peng 2,  Ao Li 6,  Xiaomin Song 2,  Hao Li 7,  Dianqing Wu 8,  Lin Li 9
Affiliations

Affiliations

  • 1 State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.
  • 2 State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
  • 3 Department of Neurosurgery, Children's Hospital of Fudan University, Shanghai 201102, China.
  • 4 CAS Key Laboratory of Systems Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China.
  • 5 School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; CAS Key Laboratory of Systems Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China.
  • 6 Department of Pharmacology, Yale School of Medicine, New Haven, CT 208089, USA.
  • 7 Department of Neurosurgery, Children's Hospital of Fudan University, Shanghai 201102, China. Electronic address: lihao7272@163.com.
  • 8 Department of Pharmacology, Yale School of Medicine, New Haven, CT 208089, USA. Electronic address: dianqing.wu@yale.edu.
  • 9 State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China. Electronic address: lli@sibs.ac.cn.
PMID: 33186520 DOI: 10.1016/j.ccell.2020.10.009
Abstract

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.

Keywords

CXorf67; PALB2; PARP inhibitors; ependymoma tumor; homologous recombination repair; radiotherapy.

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