Evidence map›Paper›PMID 39864589›Full record

ArticleJournal of advanced research2025

Ailanthone induces triple-negative breast cancer cells death involving the inhibition of OTUB1-mediated ERRα deubiquitylation.

Ziyue Zhang, Wei Huang, Li Wang, Guanjun Li, Fang Xu, Pengfei Wu, Chuqiao Luo, Qian Huang, Wenhua Kuang, Zhengyong Liu and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of advanced research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
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

8 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Research progress of DUB enzyme in breast cancer.Clinical and experimental medicine · 2025
    Review
  7. Programmed cell death in triple-negative breast cancer.Cellular & molecular biology letters · 2025
    Review
  8. 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

17 authors.

Ziyue ZhangDepartment of Pulmonary and Critical Care Medicine, Shenzhen Institute of Respiratory Diseases, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatrics, Shenzhen People's Hospital, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong 518020, China; State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM & New Drugs Research, Center for Bioactive Natural Molecules and Innovative Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, China.
Wei HuangHubei Province Key Laboratory of Traditional Chinese Medicine Resource and Chemistry, Department of Pharmacy, Hubei University of Chinese Medicine, Hubei Shizhen Laboratory, Wuhan 430061, China; Institute for Safflower Industry Research of Shihezi University, Pharmacy College of Shihezi University, KeyLaboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, Shihezi 832003, China.
Li WangDepartment of Pulmonary and Critical Care Medicine, Shenzhen Institute of Respiratory Diseases, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatrics, Shenzhen People's Hospital, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong 518020, China; Department of Breast Surgery, Xingtai Peoples' Hospital, Xingtai 054000, China.
Guanjun LiDepartment of Pulmonary and Critical Care Medicine, Shenzhen Institute of Respiratory Diseases, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatrics, Shenzhen People's Hospital, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong 518020, China.
Fang XuState Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM & New Drugs Research, Center for Bioactive Natural Molecules and Innovative Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, China.
Pengfei WuState Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM & New Drugs Research, Center for Bioactive Natural Molecules and Innovative Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, China.
Chuqiao LuoDepartment of Pulmonary and Critical Care Medicine, Shenzhen Institute of Respiratory Diseases, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatrics, Shenzhen People's Hospital, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong 518020, China.
Qian HuangState Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM & New Drugs Research, Center for Bioactive Natural Molecules and Innovative Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, China.
Wenhua KuangDepartment of Pulmonary and Critical Care Medicine, Shenzhen Institute of Respiratory Diseases, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatrics, Shenzhen People's Hospital, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong 518020, China.
Zhengyong LiuState Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM & New Drugs Research, Center for Bioactive Natural Molecules and Innovative Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, China.
Ying JiangDepartment of Pulmonary and Critical Care Medicine, Shenzhen Institute of Respiratory Diseases, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatrics, Shenzhen People's Hospital, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong 518020, China.
Xiaoling ZhaoDepartment of Breast Surgery, Xingtai Peoples' Hospital, Xingtai 054000, China.
Yayuan ZhangDepartment of Pulmonary and Critical Care Medicine, Shenzhen Institute of Respiratory Diseases, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatrics, Shenzhen People's Hospital, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong 518020, China. Electronic address: 13699880018@163.com.
Wencai YeState Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM & New Drugs Research, Center for Bioactive Natural Molecules and Innovative Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, China. Electronic address: chywc@aliyun.com.
Juan LiHubei Province Key Laboratory of Traditional Chinese Medicine Resource and Chemistry, Department of Pharmacy, Hubei University of Chinese Medicine, Hubei Shizhen Laboratory, Wuhan 430061, China. Electronic address: lz198207@126.com.
Nan MaState Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM & New Drugs Research, Center for Bioactive Natural Molecules and Innovative Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, China. Electronic address: nanma927@126.com.
Jigang WangDepartment of Pulmonary and Critical Care Medicine, Shenzhen Institute of Respiratory Diseases, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatrics, Shenzhen People's Hospital, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong 518020, China; State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China. Electronic address: jgwang@icmm.ac.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionTriple-negative breast cancer (TNBC) remains the most aggressive subtype of breast cancer, and effective therapeutic strategies are needed. Estrogen-related receptor alpha (ERRα) is considered a promising target for managing TNBC.

objectivesHere, we aimed to screen natural products to find downregulator of ERRα and elucidate its mechanism of action.

methodsTNBC cells (MDA-MB-231, MDA-MB-468, MDA-MB-453, and BT-549) were used for in vitro studies, and a subcutaneous MDA-MB-231 tumor model was created for in vivo studies. Immunofluorescence assessed protein distribution, while competitive activity-based protein profiling identified potential target proteins. Co-immunoprecipitation detected protein interactions and modifications, and a luciferase reporter assay evaluated ERRα transcriptional activity.

resultsThe natural product Ailanthone (AIL) effectively induced cell death in TNBC cells by reducing the protein level of ERRα. The mechanism of action involved AIL promoting the degradation of ERRα through the ubiquitin-proteasome system, consequently reducing its transcriptional activity. The competitive-ABPP method mapped the profile of target proteins for AIL, and OTU domain-containing ubiquitin aldehyde-binding protein 1 (OTUB1) was identified as a pivotal target of AIL in regulating ERRα protein levels. OTUB1 was validated as a novel deubiquitinating enzyme for ERRα, with its C91 residue being crucial for this deubiquitination process. AIL was found to inhibit the enzyme activity of OTUB1 by interacting with the C91 residue and disrupt the interaction between OTUB1 and ERRα, ultimately leading to the inhibition of ERRα.

conclusionAIL is a promising downregulator of ERRα, and the mechanism of this downregulation has been elucidated. Additionally, a new regulatory relationship between ERRα and OTUB1 is identified. The research presented in this article is anticipated to yield potential lead compounds for ERRα regulatory agents and to stimulate the development of novel therapeutic strategies designed to modulate ERRα activity for the treatment of TNBC.

Indexed as

Cysteine EndopeptidasesReceptors, EstrogenTriple Negative Breast NeoplasmsAnimalsCell DeathCell Line, TumorDeubiquitinating EnzymesERRalpha Estrogen-Related ReceptorFemaleHumansMiceUbiquitinationXenograft Model Antitumor AssaysCysteine EndopeptidasesDeubiquitinating EnzymesERRalpha Estrogen-Related ReceptorOTUB1 protein, humanReceptors, EstrogenChemical biologyDrug targetNatural productsProteomics

Identifiers

PMID39864589
PMCPMC12627351

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