Evidence map›Paper›PMID 41168787›Full record

ArticleBMC medical genomics2025

The role of TEAD4 gene in the Hippo signaling pathway in triple-negative breast cancer and targeted therapy strategies.

Xueliang Zhang, Tao Wang, Xiaowen Lian, Changsheng Wei, Dong Yan, Yan Liang

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Article in BMC medical genomics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1citing papers in PubMed
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1 · What the graph read from it

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3 · Its place in the literature

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1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Xueliang ZhangDepartment of Medical Oncology, Sun Yat-sen University Cancer Center Gansu Hospital, Lanzhou, 730050, China.
Tao WangCentre for Translational Medicine, Gansu Provincial Academic Institute for Medical Research, Lanzhou, 730050, China.
Xiaowen LianDepartment of Medicine Biotechnology, Gansu Provincial Academic Institute for Medical Research, Lanzhou, 730050, China.
Changsheng WeiDepartment of Breast Surgery, Sun Yat-sen University Cancer Center Gansu Hospital, Lanzhou, 730050, China.
Dong YanDepartment of Medical Oncology, Sun Yat-sen University Cancer Center Gansu Hospital, Lanzhou, 730050, China.
Yan LiangDepartment of Breast Surgery, Sun Yat-sen University Cancer Center Gansu Hospital, Lanzhou, 730050, China. yanliangGSZL@163.com.

Funding

Gansu Provincial Health and Medical Research Program GSWSKY2020-04Key Research and Development Project of the Gansu Province Science and Technology Plan 22YF7FA099
6 · The paper itself

Abstract

backgroundTriple-negative breast cancer (TNBC) is an aggressive subtype with poor prognosis and limited targeted therapies. The Hippo signaling pathway, critical in tumor progression, may harbor key genes influencing TNBC behavior. However, the specific genes and their clinical significance remain unclear.

methodsWe analyzed the GSE45827 dataset from the GEO database using differential gene expression analysis (DEG) and weighted gene co-expression network analysis (WGCNA) to identify TNBC-related genes. We enriched Hippo pathway-related genes from the MsigDB database and literature to identify candidate genes (HRGs) that may affect TNBC progression. The Boruta algorithm further screened for core genes, which were validated by immunohistochemistry in TNBC and other breast cancer tissues. Finally, we explored the biological and pharmacological significance of the target through drug prediction, molecular docking, molecular dynamics simulations, and in vitro experiments.

resultsDEG analysis identified 2,888 differentially expressed genes, and WGCNA yielded 276 TNBC-associated genes. Intersection analysis with 70 hypoxia-related genes (HRGs) revealed four key genes: TEAD4, WWTR1, AREG, and SOX11. TEAD4 was confirmed as the central gene influencing TNBC progression. Immunohistochemical results showed strong TEAD4 expression in TNBC tissues, with negligible expression in adjacent normal tissues or other breast cancer subtypes. Drug prediction and molecular docking identified irinotecan as a potential TEAD4-targeting agent. Molecular dynamics simulations confirmed the stable binding and favorable dynamics of the irinotecan-TEAD4 complex. Both TEAD4 knockdown and irinotecan treatment significantly suppressed TNBC cell migration and invasion. The combination of TEAD4 knockout and irinotecan produced a more pronounced inhibitory effect, underscoring the therapeutic potential of targeting TEAD4 in TNBC.

conclusionsThrough comprehensive analysis, we identified TEAD4 as a key gene in TNBC with high expression specificity. Irinotecan may be a potential targeted drug for TEAD4, offering a new therapeutic strategy for TNBC and potentially improving patient outcomes. Further experimental verification is required.

Indexed as

DNA-Binding ProteinsMuscle ProteinsProtein Serine-Threonine KinasesSignal TransductionTranscription FactorsTriple Negative Breast NeoplasmsCell Line, TumorFemaleGene Expression Regulation, NeoplasticHippo Signaling PathwayHumansMolecular Docking SimulationMolecular Targeted TherapyTEA Domain Transcription FactorsDNA-Binding ProteinsMuscle ProteinsProtein Serine-Threonine KinasesTEAD4 protein, humanTEA Domain Transcription FactorsTranscription FactorsHippo signaling pathwayIrinotecanTargeted therapyTEAD4Triple-negative breast cancer

Identifiers

PMID41168787
PMCPMC12573850

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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.