2. Academic Validation
  3. Stromal PLAU mediates tumor progression and informs a novel therapeutic target in triple-negative breast cancer

Stromal PLAU mediates tumor progression and informs a novel therapeutic target in triple-negative breast cancer

  • Cancer Cell Int. 2025 Jul 11;25(1):259. doi: 10.1186/s12935-025-03867-y.
Jun Zou 1,  Jingyao Zhang 2,  Yu Li 2,  Baowen Yuan 2,  Yuanyi Wang 1,  Yalong Qi 1,  Qian Wang 3,  Wan Qin 4,  Xianglin Yuan 5,  Binghe Xu 6
Affiliations

Affiliations

  • 1 Department of Medical Oncology, National Clinical Research Center for Cancer, Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
  • 2 State Key Laboratory of Molecular Oncology, National Cancer Center, National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
  • 3 Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
  • 4 Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. wanqinhust@hotmail.com.
  • 5 Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. yuanxianglin@hust.edu.cn.
  • 6 Department of Medical Oncology, National Clinical Research Center for Cancer, Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. xubinghe@medmail.com.cn.
PMID: 40646496 DOI: 10.1186/s12935-025-03867-y
Abstract

Triple-negative breast Cancer (TNBC) is an aggressive subtype characterized by limited treatment options and poor prognosis. Recent evidence highlights the crucial role of cancer-associated fibroblasts (CAFs) in TNBC progression, yet their molecular characteristics remain incompletely understood. In this study, we performed a comprehensive analysis combining bioinformatics approaches with experimental validation to investigate CAF-related genes in TNBC. Using weighted gene co-expression network analysis (WGCNA) of TNBC samples from TCGA and METABRIC datasets, we identified 185 CAF-related genes significantly associated with extracellular matrix organization and TGF-β signaling pathways. Through rigorous statistical modeling, we developed a 3-gene prognostic signature (CERCAM, JAM3, PLAU) that effectively stratified TNBC patients into high- and low-risk groups with distinct survival outcomes. Importantly, we validated the functional role of PLAU, one of the signature genes, through in vitro and in vivo experiments. Results showed that CAF-derived PLAU played key role in the malignant behaviors of TNBC. Our findings provide new insights into CAF-mediated TNBC progression and suggest potential stromal targets for therapeutic intervention.

Keywords

Cancer-associated fibroblasts; PLAU; Prognostic signature; TNBC; Tumor microenvironment.

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