Evidence map›Paper›PMID 33571129›Full record

ArticleScience advances2021

Genome-wide CRISPR-Cas9 screen identified KLF11 as a druggable suppressor for sarcoma cancer stem cells.

Yicun Wang, Jinhui Wu, Hui Chen, Yang Yang, Chengwu Xiao, Xiaoming Yi, Changjie Shi, Ke Zhong, Haowei He, Yaoming Li and 16 more

Open access · goldAbstract read
In one paragraph

Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

22 citing papers in PubMed, 38 citations in OpenAlex.

  1. Article
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  8. Article
  9. Review
  10. KLF transcription factors in bone diseases.Journal of cellular and molecular medicine · 2024
    Review
  11. Article
  12. Article
  13. Article
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  15. Article
  16. Review
  17. Article
  18. Article
  19. Kruppel-like Factors in Skeletal Physiology and Pathologies.International journal of molecular sciences · 2022
    Review
  20. Review
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

26 authors at 7 institutions in 2 countries.

Yicun WangDepartment of Urology, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing 210002, China.ORCID 0000-0003-4067-1637
Jinhui WuDepartment of Orthopedic, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.ORCID 0000-0001-7158-2296
Hui ChenDepartment of Pathology, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing 210002, China.ORCID 0000-0002-7901-0759
Yang YangInstitute of Clinical Laboratory Medicine, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing 210002, China.ORCID 0000-0001-9887-0685
Chengwu XiaoDepartment of Urology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.ORCID 0000-0002-1013-0429
Xiaoming YiDepartment of Urology, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing 210002, China.
Changjie ShiDepartment of Urology, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing 210002, China.
Ke ZhongDepartment of Urology, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing 210002, China.
Haowei HeDepartment of Urology, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing 210002, China.ORCID 0000-0002-0358-4983
Yaoming LiDepartment of Urology, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
Zhenjie WuDepartment of Urology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.ORCID 0000-0002-6487-5207
Guangxin ZhouDepartment of Orthopedic, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing 210002, China.
Qiu RaoDepartment of Pathology, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing 210002, China.
Xiaoxia WangDepartment of Pathology, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing 210002, China.
Xiaodie ZhouDepartment of Pathology, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing 210002, China.
Gwen LomberkDepartment of Surgery, Medical College of Wisconsin Milwaukee, WI 53226, USA.
Bing LiuDepartment of Urology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
Jianning ZhaoDepartment of Orthopedic, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing 210002, China.
Jingping GeDepartment of Urology, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing 210002, China. septsoul@hotmail.com shzwqzsl@163.com gjp_doctor@qq.com chuxiaoyuan000@163.com chencheng1289@126.com zhouxuhui@smmu.edu.cn wanglinhui@smmu.edu.cn.ORCID 0000-0002-4464-3230
Wenquan ZhouDepartment of Urology, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing 210002, China. septsoul@hotmail.com shzwqzsl@163.com gjp_doctor@qq.com chuxiaoyuan000@163.com chencheng1289@126.com zhouxuhui@smmu.edu.cn wanglinhui@smmu.edu.cn.ORCID 0000-0002-5519-9235
Xiaoyuan ChuDepartment of Medical Oncology, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing 210002, China. septsoul@hotmail.com shzwqzsl@163.com gjp_doctor@qq.com chuxiaoyuan000@163.com chencheng1289@126.com zhouxuhui@smmu.edu.cn wanglinhui@smmu.edu.cn.ORCID 0000-0002-7917-7874
Cheng ChenDepartment of Medical Oncology, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing 210002, China. septsoul@hotmail.com shzwqzsl@163.com gjp_doctor@qq.com chuxiaoyuan000@163.com chencheng1289@126.com zhouxuhui@smmu.edu.cn wanglinhui@smmu.edu.cn.ORCID 0000-0001-6405-7733
Xuhui ZhouDepartment of Orthopedic, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China. septsoul@hotmail.com shzwqzsl@163.com gjp_doctor@qq.com chuxiaoyuan000@163.com chencheng1289@126.com zhouxuhui@smmu.edu.cn wanglinhui@smmu.edu.cn.ORCID 0000-0002-8026-5468
Linhui WangDepartment of Urology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China. septsoul@hotmail.com shzwqzsl@163.com gjp_doctor@qq.com chuxiaoyuan000@163.com chencheng1289@126.com zhouxuhui@smmu.edu.cn wanglinhui@smmu.edu.cn.ORCID 0000-0002-4056-0462
Kunliang GuanDepartment of Pharmacology and Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA.ORCID 0000-0003-1892-0174
Le QuDepartment of Urology, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing 210002, China. septsoul@hotmail.com shzwqzsl@163.com gjp_doctor@qq.com chuxiaoyuan000@163.com chencheng1289@126.com zhouxuhui@smmu.edu.cn wanglinhui@smmu.edu.cn.ORCID 0000-0001-9499-4277
Second Affiliated Hospital of Nanjing Medical University · CNSecond Military Medical University · CNNanjing General Hospital of Nanjing Military Command · CNArmy Medical University · CNJinling Institute of Technology · CNMedical College of Wisconsin · USUniversity of California San Diego · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cancer stem cells (CSCs) are involved in tumorigenesis, recurrence, and therapy resistance. To identify critical regulators of sarcoma CSCs, we performed a reporter-based genome-wide CRISPR-Cas9 screen and uncovered Kruppel-like factor 11 (KLF11) as top candidate. In vitro and in vivo functional annotation defined a negative role of KLF11 in CSCs. Mechanistically, KLF11 and YAP/TEAD bound to adjacent DNA sites along with direct interaction. KLF11 recruited SIN3A/HDAC to suppress the transcriptional output of YAP/TEAD, which, in turn, promoted KLF11 transcription, forming a negative feedback loop. However, in CSCs, this negative feedback was lost because of epigenetic silence of KLF11, causing sustained YAP activation. Low KLF11 was associated with poor prognosis and chemotherapy response in patients with sarcoma. Pharmacological activation of KLF11 by thiazolidinedione effectively restored chemotherapy response. Collectively, our study identifies KLF11 as a negative regulator in sarcoma CSCs and potential therapeutic target.

Indexed as

CRISPR-Cas SystemsSarcomaApoptosis Regulatory ProteinsHumansNeoplastic Stem CellsRepressor ProteinsApoptosis Regulatory ProteinsKLF11 protein, humanRepressor Proteins

Identifiers

PMID33571129
PMCPMC7840125
OpenAlexW3029881948

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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.