Evidence map›Paper›PMID 33005030›Full record

ArticleNature cell biology2020

LRRC31 inhibits DNA repair and sensitizes breast cancer brain metastasis to radiation therapy.

Yanke Chen, Ting Jiang, Hongyi Zhang, Xingchun Gou, Cong Han, Jianhui Wang, Ann T Chen, Jun Ma, Jun Liu, Zeming Chen and 11 more

Open access · greenAbstract read
In one paragraph

Article in Nature cell biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
5.6field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

51 citing papers in PubMed, 74 citations in OpenAlex.

  1. Trial
  2. mCell death and differentiation · 2026
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  14. Biological profile of breast cancer brain metastasis.Acta neuropathologica communications · 2025
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors at 6 institutions in 2 countries.

Yanke Chen *Department of Cell Biology and Genetics, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Ting Jiang *Department of Cell Biology and Genetics, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Hongyi Zhang *Department of Neurosurgery, Yale University, New Haven, CT, USA.
Xingchun Gou *Department of Neurosurgery, Yale University, New Haven, CT, USA.
Cong HanDepartment of Cell Biology and Genetics, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Jianhui WangDepartment of Pathology, Yale University, New Haven, CT, USA.
Ann T ChenDepartment of Biomedical Engineering, Yale University, New Haven, CT, USA.
Jun MaDepartment of Radiology in the First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Jun LiuDepartment of Neurosurgery, Yale University, New Haven, CT, USA.
Zeming ChenDepartment of Neurosurgery, Yale University, New Haven, CT, USA.
Xintao JingDepartment of Cell Biology and Genetics, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Hong LeiShaanxi Key Laboratory of Brain Disorders & Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, China.
Zhenzhen WangDepartment of Cell Biology and Genetics, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Youmei BaoDepartment of Neurosurgery, Yale University, New Haven, CT, USA.
Mehdi BaqriDepartment of Neurosurgery, Yale University, New Haven, CT, USA.
Yong ZhuSchool of Public Health, Yale University, New Haven, CT, USA.
Ranjit S BindraDepartment of Therapeutic Radiology, Yale University, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-3255-0467
James E HansenDepartment of Therapeutic Radiology, Yale University, New Haven, CT, USA.
Jun DouDepartment of Pathogenic Biology and Immunology, School of Medicine, Southeast University, Nanjing, China.
Chen HuangDepartment of Cell Biology and Genetics, Xi'an Jiaotong University, Xi'an, Shaanxi, China. hchen@mail.xjtu.edu.cn.ORCID http://orcid.org/0000-0002-2407-9716
Jiangbing ZhouDepartment of Neurosurgery, Yale University, New Haven, CT, USA. jiangbing.zhou@yale.edu.ORCID http://orcid.org/0000-0002-1201-5360
Yale University · USXi'an Jiaotong University · CNFirst Affiliated Hospital of Xi'an Jiaotong University · CNJinan University · CNSoutheast University · CNXi'an Medical University · CN

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Systemic gene therapy for glioblastomaR01NS095817 · NINDS · YALE UNIVERSITY · PI ZHOU, JIANGBING · 2016 to 2020
$1.8M
NCATS NIH HHS UL1 TR001863NINDS NIH HHS R01 NS095817
6 · The paper itself

Abstract

Breast cancer brain metastasis (BCBM) is a devastating disease. Radiation therapy remains the mainstay for treatment of this disease. Unfortunately, its efficacy is limited by the dose that can be safely applied. One promising approach to overcoming this limitation is to sensitize BCBMs to radiation by inhibiting their ability to repair DNA damage. Here, we report a DNA repair suppressor, leucine-rich repeat-containing protein 31 (LRRC31), that was identified through a genome-wide CRISPR screen. We found that overexpression of LRRC31 suppresses DNA repair and sensitizes BCBMs to radiation. Mechanistically, LRRC31 interacts with Ku70/Ku80 and the ataxia telangiectasia mutated and RAD3-related (ATR) at the protein level, resulting in inhibition of DNA-dependent protein kinase, catalytic subunit (DNA-PKcs) recruitment and activation, and disruption of the MutS homologue 2 (MSH2)-ATR module. We demonstrate that targeted delivery of the LRRC31 gene via nanoparticles improves the survival of tumour-bearing mice after irradiation. Collectively, our study suggests LRRC31 as a major DNA repair suppressor that can be targeted for cancer radiosensitizing therapy.

Indexed as

DNA DamageDNA RepairAnimalsApoptosisAtaxia Telangiectasia Mutated ProteinsBrain NeoplasmsBreast NeoplasmsCell ProliferationFemaleGamma RaysHumansMiceMice, Inbred BALB CMice, NudeMutS Homolog 2 ProteinNuclear ProteinsAtaxia Telangiectasia Mutated ProteinsATR protein, humanLRRC31 protein, humanMSH2 protein, humanMutS Homolog 2 ProteinNuclear ProteinsRadiation-Sensitizing Agents

Identifiers

PMID33005030
PMCPMC7962994
OpenAlexW3090626360

What OpenQuestion holds

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LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.