Stromal PLAU mediates tumor progression and informs a novel therapeutic target in triple-negative breast cancer
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 under...
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| Format: | Article |
| Language: | English |
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BMC
2025-07-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-025-03867-y |
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| author | Jun Zou Jingyao Zhang Yu Li Baowen Yuan Yuanyi Wang Yalong Qi Qian Wang Wan Qin Xianglin Yuan Binghe Xu |
| author_facet | Jun Zou Jingyao Zhang Yu Li Baowen Yuan Yuanyi Wang Yalong Qi Qian Wang Wan Qin Xianglin Yuan Binghe Xu |
| author_sort | Jun Zou |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-a898f846bd5f43ecaf46b3d9fe0e869d |
| institution | Kabale University |
| issn | 1475-2867 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj-art-a898f846bd5f43ecaf46b3d9fe0e869d2025-08-20T03:42:10ZengBMCCancer Cell International1475-28672025-07-0125111610.1186/s12935-025-03867-yStromal PLAU mediates tumor progression and informs a novel therapeutic target in triple-negative breast cancerJun Zou0Jingyao Zhang1Yu Li2Baowen Yuan3Yuanyi Wang4Yalong Qi5Qian Wang6Wan Qin7Xianglin Yuan8Binghe Xu9Department of Medical Oncology, National Clinical Research Center for Cancer, Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical CollegeState Key Laboratory of Molecular Oncology, National Cancer Center, National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical CollegeState Key Laboratory of Molecular Oncology, National Cancer Center, National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical CollegeState Key Laboratory of Molecular Oncology, National Cancer Center, National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical CollegeDepartment of Medical Oncology, National Clinical Research Center for Cancer, Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Medical Oncology, National Clinical Research Center for Cancer, Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Medical Oncology, National Clinical Research Center for Cancer, Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical CollegeAbstract 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.https://doi.org/10.1186/s12935-025-03867-yTNBCCancer-associated fibroblastsPrognostic signaturePLAUTumor microenvironment |
| spellingShingle | Jun Zou Jingyao Zhang Yu Li Baowen Yuan Yuanyi Wang Yalong Qi Qian Wang Wan Qin Xianglin Yuan Binghe Xu Stromal PLAU mediates tumor progression and informs a novel therapeutic target in triple-negative breast cancer Cancer Cell International TNBC Cancer-associated fibroblasts Prognostic signature PLAU Tumor microenvironment |
| title | Stromal PLAU mediates tumor progression and informs a novel therapeutic target in triple-negative breast cancer |
| title_full | Stromal PLAU mediates tumor progression and informs a novel therapeutic target in triple-negative breast cancer |
| title_fullStr | Stromal PLAU mediates tumor progression and informs a novel therapeutic target in triple-negative breast cancer |
| title_full_unstemmed | Stromal PLAU mediates tumor progression and informs a novel therapeutic target in triple-negative breast cancer |
| title_short | Stromal PLAU mediates tumor progression and informs a novel therapeutic target in triple-negative breast cancer |
| title_sort | stromal plau mediates tumor progression and informs a novel therapeutic target in triple negative breast cancer |
| topic | TNBC Cancer-associated fibroblasts Prognostic signature PLAU Tumor microenvironment |
| url | https://doi.org/10.1186/s12935-025-03867-y |
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