Evidence map›Paper›PMID 41716632›Full record

ArticleGenes & diseases2026

NRG4 suppresses breast cancer metastasis via ERBB4-YAP1-mediated down-regulation of MMPs.

Saijun Wang, Mingwei Guo, Lingyun Xu, Jiaming Xue, Shuai Chen, Ke Xu, Yan Zhou, Aihua Gu, Wei Gao, Jianwei Zhou and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Genes & diseases, 2026. 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. Article
  2. Article
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

13 authors.

Saijun WangDepartment of Gastrointestinal Surgery, Changzhou Medical Center, The Third Affiliated Hospital of Nanjing Medical University, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Nanjing Medical University, Changzhou, Jiangsu 213000, China.
Mingwei GuoShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, Shanghai 200241, China.
Lingyun XuDepartment of Breast Surgery, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, The Third Affiliated Hospital of Nanjing Medical University, Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu 213000, China.
Jiaming XueDepartment of Gastrointestinal Surgery, Changzhou Medical Center, The Third Affiliated Hospital of Nanjing Medical University, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Nanjing Medical University, Changzhou, Jiangsu 213000, China.
Shuai ChenDepartment of Gastrointestinal Surgery, Changzhou Medical Center, The Third Affiliated Hospital of Nanjing Medical University, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Nanjing Medical University, Changzhou, Jiangsu 213000, China.
Ke XuKey Laboratory of Human Functional Genomics of Jiangsu Province, National Health Commission Key Laboratory of Antibody Techniques, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
Yan ZhouDepartment of Gastrointestinal Surgery, Changzhou Medical Center, The Third Affiliated Hospital of Nanjing Medical University, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Nanjing Medical University, Changzhou, Jiangsu 213000, China.
Aihua GuState Key Laboratory of Reproductive Medicine, School of Public Health, Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
Wei GaoKey Laboratory of Human Functional Genomics of Jiangsu Province, National Health Commission Key Laboratory of Antibody Techniques, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
Jianwei ZhouKey Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
Yi ZhangShanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Centre for Diabetes, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China.
Liming TangDepartment of Gastrointestinal Surgery, Changzhou Medical Center, The Third Affiliated Hospital of Nanjing Medical University, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Nanjing Medical University, Changzhou, Jiangsu 213000, China.
Dongmei WangDepartment of Gastrointestinal Surgery, Changzhou Medical Center, The Third Affiliated Hospital of Nanjing Medical University, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Nanjing Medical University, Changzhou, Jiangsu 213000, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Obesity exacerbates breast cancer metastasis, yet the underlying mechanisms remain incompletely understood. Here, we identify neuregulin 4 (NRG4), a ligand of Erb-B2 receptor tyrosine kinase 4 (ERBB4), as a key regulator of metastasis, through the ERBB4-YAP1 signaling axis. Using MMTV-PyMT and 4T1 breast cancer models, we demonstrate that obesity accelerates metastasis, while NRG4, secreted by inguinal white adipose tissue (iWAT), inhibits cancer cell migration and epithelial-mesenchymal transition (EMT). Mechanistically, NRG4 activates ERBB4, producing a cleaved pERBB4 fragment that interacts with phosphorylated YAP1 (pYAP1), restricting its nuclear translocation. RNA sequencing revealed that NRG4 suppressed the transcription of Mmp9 and Mmp12, which encode matrix metalloproteinases critical for extracellular matrix remodeling and invasion. Co- immunoprecipitation and promoter assay confirmed that YAP1 bound to TEAD1 and activated MMP9/MMP12 transcription in the absence of NRG4. Importantly, recombinant NRG4 (rNRG4) reduced the growth and invasiveness of breast cancer organoids. These findings establish NRG4 as a metastasis suppressor in obesity-associated breast cancer by inhibiting the ERBB4-YAP1 pathway and down-regulating matrix metalloproteinases. Our study highlights the therapeutic potential of targeting NRG4-ERBB4 signaling to mitigate obesity-driven breast cancer progression.

Indexed as

Breast cancerEpithelial–mesenchymal transitionMatrix metalloproteinase alterationsNeuregulin 4YAP

Identifiers

PMID41716632
PMCPMC12914539

What Socratic holds

Textmetadata
LicenceCC BY
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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 Socratic graph.