ArticleMolecular cancer2016
Higher levels of TIMP-1 expression are associated with a poor prognosis in triple-negative breast cancer.
Article in Molecular cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
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Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 154 citations in OpenAlex.
- Diagnostic Accuracy of Blood-based Biomarkers for Pancreatic Cancer: A Systematic Review and Meta-analysis.Cancer research communications · 2022Pooled it
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- Single-cell profiling reveals a novel CAF subpopulation linking stromal heterogeneity to immune suppression in breast cancer subtypes.Journal of translational medicine · 2026Article
- Bioinformatic Analysis of Contrasting Expression Patterns and Molecular Interactions of TIMPs in Breast Cancer: Implications for Tumor Progression and Survival.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026Article
- The Great Potential of DNA Methylation in Triple-Negative Breast Cancer: From Biological Basics to Clinical Application.Biomedicines · 2026Review
- Multimodal profiling of pancreatic cancer reveals a TIMP-1-dominated secretory profile determining pro-tumor immunoinstruction in human cancers.Cell reports. Medicine · 2026Article
- Treadmill exercise ameliorates atherogenesis and vascular inflammation in ApoEScientific reports · 2025Article
- Loss of TRPV4 reduces pancreatic cancer growth and metastasis.JCI insight · 2025Article
- The Role of Extracellular Proteases and Extracellular Matrix Remodeling in the Pre-Metastatic Niche.Biomolecules · 2025Review
- stImage: a versatile framework for optimizing spatial transcriptomic analysis through customizable deep histology and location informed integration.Briefings in bioinformatics · 2025Article
- Spatial transcriptomics of progression gene signature and tumor microenvironment leading to progression in mycosis fungoides.Blood advances · 2025Article
- Comparison Bioinformatic Analysis of Extracellular Vesicles-Related Genes and MicroRNAs in Breast Cancer.International journal of molecular sciences · 2025Article
- Angiogenesis related gene signatures predict prognosis and guide therapeutic strategies in renal clear cell carcinoma.Scientific reports · 2025Article
- TIMP1 Overexpression in Ovarian Cancer Spheroids: Implications for Prognosis, Resistance, and Metastatic Potential.Cancers · 2025Article
- Proteomics uncovers ICAM2 (CD102) as a novel serum biomarker of proliferative lupus nephritis.Lupus science & medicine · 2025Article
- Glioblastoma drives protease-independent extracellular matrix invasion of microglia.Materials today. Bio · 2025Article
- Integrative network pharmacology, transcriptomics, and proteomics reveal the material basis and mechanism of the Shen Qing Weichang Formula against gastric cancer.Chinese medicine · 2025Article
- Identification of MAPK12 as a Prognostic Biomarker for Esophageal Carcinoma Using Bioinformatics and Machine Learning.BioMed research international · 2025Article
- ERK3/MAPK6 promotes triple-negative breast cancer progression through collective migration and EMT plasticity.Frontiers in oncology · 2025Article
- Transcription Factor FOSL1 Promotes Angiogenesis of Colon Carcinoma by Regulating the VEGF Pathway Through Activating TIMP1.Biochemical genetics · 2024Article
3 more citing papers are in PubMed but not listed here.
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6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTissue inhibitor of metalloproteinases-1 (TIMP-1) is a multifunctional protein that can directly regulate apoptosis and metastasis. In this study, we investigated the functional and molecular mechanisms by which TIMP-1 influences triple-negative breast cancer (TNBC).
methodsThe expression level of TIMP-1 in breast cancer tissues was analyzed using the ONCOMINE microarray database. The overall survival of patients with distinct molecular subtypes of breast cancer stratified by TIMP-1 expression levels was evaluated using Kaplan-Meier analysis. Bisulfate sequencing PCR (BSP) was used to analyze the methylation status of the TIMP-1 promoter. Real-time-PCR (RT-PCR), Western blot and ELISA assays were used to evaluate gene and protein expression in cell lines and human tissue specimens. In addition, TIMP-1 function was analyzed using a series of in vitro and in vivo assays with cells in which TIMP-1 was inhibited using RNAi or neutralizing antibodies.
resultsWe found that serum TIMP-1 levels were strongly enhanced in patients with TNBC and that elevated TIMP-1 levels were associated with a poor prognosis in TNBC. However, TIMP-1 levels were not significantly associated with overall survival in other subtypes of breast cancer or in the overall population of breast cancer patients. We also report the first evidence that the TIMP-1 promoter is hypomethylated in TNBC cell lines compared with non-TNBC cell lines, suggesting that aberrant TIMP-1 expression in TNBC results from reduced DNA methylation. RNAi-mediated silencing of TIMP-1 in TNBC cells induced cell cycle arrest at the G1 phase and reduced cyclin D1 expression. In addition, mechanistic analyses revealed that the p-Akt and p-NF-κB signaling pathways, but not the GSK-3β and MAPK1/2 pathways, are associated with TIMP-1 overexpression in TNBC cells. Moreover, neutralizing antibodies against TIMP-1 significantly decreased the rate of tumor growth in vivo.
conclusionsOur findings suggest that TIMP-1 is a biomarker indicative of a poor prognosis in TNBC patients and that targeting TIMP-1 may provide an attractive therapeutic intervention specifically for triple-negative breast cancer patients.
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