Evidence map›Paper›PMID 39641870›Full record

ArticleJournal of molecular histology2024

DYRK2 controls GSTPI expression through ubiquitination and degradation of Twist1 to reduce chemotherapy resistance caused by EMT in breast cancer.

Guofa Xu, MeiYu Zhou, Qian Li, YanYan Li, Chong Zhang, Zailiang Yang

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In one paragraph

Article in Journal of molecular histology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. 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

6 authors.

Guofa XuThe Comprehensive Cancer Center, Chongqing University Fuling Hospital, No.2 Gaosuntang Road, Fuling District, 408000, Chongqing, P.R. China.
MeiYu ZhouThe Comprehensive Cancer Center, Chongqing University Fuling Hospital, No.2 Gaosuntang Road, Fuling District, 408000, Chongqing, P.R. China.
Qian LiDepartment of Occupational Disease and Poisoning Medicine,The First Affiliated Hospital of Chongqing Medical and pharmaceutical College, 400060, Chongqing, P.R. China.
YanYan LiThe Comprehensive Cancer Center, Chongqing University Fuling Hospital, No.2 Gaosuntang Road, Fuling District, 408000, Chongqing, P.R. China.
Chong ZhangDepartment of Pathology, Chongqing University Fuling Hospital, 408000, Chongqing, P.R. China.
Zailiang YangThe Comprehensive Cancer Center, Chongqing University Fuling Hospital, No.2 Gaosuntang Road, Fuling District, 408000, Chongqing, P.R. China. yangzailiang408000@cqu.edu.cn.

Funding

Natural Science Foundation Project of Chongqing, Chongqing Science and Technology Commission CSTB2022NSCQ-MSX1362
6 · The paper itself

Abstract

backgroundBreast cancer (BC) poses a significant global health challenge, with chemotherapy resistance, especially to docetaxel, remaining a major obstacle in effective treatment. The molecular mechanisms underlying this resistance are critical for developing targeted therapeutic strategies.

objectiveThis study aims to explore the role of dual-specificity tyrosine phosphorylation-regulated kinase 2 (DYRK2), a member of the DYRK family, in docetaxel resistance in breast cancer cells and investigate its impact on cellular responses, including drug sensitivity and migration. Additionally, potential interactions between DYRK2 and Twist1, associated with epithelial-mesenchymal transition (EMT) and drug resistance, are explored.

methodsDocetaxel-resistant breast cancer cells were induced, and the expression levels of DYRK2, Twist1, and related genes were evaluated using real-time PCR and Western blotting. Lentivirus-mediated DYRK2 overexpression was employed to assess its effect on drug sensitivity, migratory ability, and Twist1 expression. The relationship between DYRK2 and Twist1 was examined, focusing on Twist1 ubiquitination. The impact of Twist1 on chemotherapy resistance and its binding to the Glutathione S-transferase Pi 1 (GSTP1) promoter were also investigated.

resultsDocetaxel-resistant cells exhibited down-regulated DYRK2 and up-regulated Twist1 expression. DYRK2 overexpression reversed drug resistance, decreased migration, and attenuated Twist1 and GST-π expression. DYRK2 was found to suppress Twist1 expression through ubiquitination, supported by decreased Twist1 phosphorylation and increased ubiquitination after DYRK2 overexpression. Twist1 overexpression counteracted DYRK2-induced drug sensitivity enhancement, promoting GST-π expression, EMT, migration, and proliferation. Twist1 was shown to bind to the GSTP1 promoter, enhancing its transcription. In vivo experiments confirmed DYRK2's ability to suppress chemoresistance in breast cancer cells.

conclusionDYRK2 plays a pivotal role in overcoming docetaxel resistance in breast cancer cells by suppressing Twist1 expression through ubiquitination, impacting downstream signaling and cellular responses. This study provides valuable insights for developing targeted therapies to improve breast cancer treatment outcomes.

Indexed as

Breast NeoplasmsDocetaxelDrug Resistance, NeoplasmDyrk KinasesEpithelial-Mesenchymal TransitionGene Expression Regulation, NeoplasticNuclear ProteinsProtein Serine-Threonine KinasesProtein-Tyrosine KinasesTwist-Related Protein 1UbiquitinationAnimalsCell Line, TumorCell MovementFemaleGlutathione S-Transferase piDocetaxelDyrk KinasesGlutathione S-Transferase piGSTP1 protein, humanNuclear ProteinsProtein Serine-Threonine KinasesProtein-Tyrosine KinasesTWIST1 protein, humanTwist-Related Protein 1Breast cancerDYRK2Epithelial-mesenchymal transitionGSTPITwist1

Identifiers

PMID39641870

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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.