ArticlePloS one2013
TIMP-1 promotes accumulation of cancer associated fibroblasts and cancer progression.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 198 citations in OpenAlex.
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- Manipulation with Mutational Status of VHL Regulates Hypoxic Metabolism and Pro-Angiogenic Phenotypes in ccRCC Caki-1 Cells.International journal of molecular sciences · 2025Article
- The Role of the TIMP1/LINC01615 Axis as a Regulator of the EMT Pathway in Gastric Cancer.Biological procedures online · 2025Article
- Spatial transcriptomics of progression gene signature and tumor microenvironment leading to progression in mycosis fungoides.Blood advances · 2025Article
- Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) Expression and Its Prognostic Significance in Oral Cancer Patients.Journal of maxillofacial and oral surgery · 2025Article
- Development and Validation of an Extracellular Matrix Gene Expression Signature for Prognostic Prediction in Patients with Uveal Melanoma.International journal of molecular sciences · 2025Article
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- Pan-cancer secreted proteome and skeletal muscle regulation: insight from a proteogenomic data-driven knowledge base.Functional & integrative genomics · 2025Review
- Tissue inhibitor of metalloproteinase 1 as a biomarker of venous invasion in pancreatic ductal adenocarcinoma.American journal of cancer research · 2025Article
- Transcription Factor FOSL1 Promotes Angiogenesis of Colon Carcinoma by Regulating the VEGF Pathway Through Activating TIMP1.Biochemical genetics · 2024Article
- Epigenetic and proteomic signatures associate with clonal hematopoiesis expansion rate.Nature aging · 2024Article
- Advancements in 3D In Vitro Models for Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- The TIMP protein family: diverse roles in pathophysiology.American journal of physiology. Cell physiology · 2024Review
- Identification of a novel macrophage-related prognostic signature in colorectal cancer.Scientific reports · 2024Article
- Quantification of putative ovarian cancer serum protein biomarkers using a multiplexed targeted mass spectrometry assay.Clinical proteomics · 2024Article
- The role of cancer-associated fibroblasts in the invasion and metastasis of colorectal cancer.Frontiers in cell and developmental biology · 2024Review
- Cellular Responses to Extracellular Vesicles as Potential Markers of Colorectal Cancer Progression.International journal of molecular sciences · 2023Article
- Novel CAF-identifiers via transcriptomic and protein level analysis in HNSC patients.Scientific reports · 2023Article
- Characterizing 3T3-L1 MBX Adipocyte Cell Differentiation Maintained with Fatty Acids as an In Vitro Model to Study the Effects of Obesity.Life (Basel, Switzerland) · 2023Article
20 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Treatment options for late stage prostate and colon cancer are limited and there is an urgent need to develop more effective and targeted novel therapies, which starts with identification and validation of novel therapeutic targets. Recent clinical studies have demonstrated that tissue inhibitor matrix metalloproteinase-1 (TIMP-1) levels are elevated in cancer patient plasma and elevated TIMP-1 levels are associated with worse clinical outcomes. However, it is unknown whether TIMP-1 serves merely as a biomarker of cancer progression or has a functional role in promoting cancer progression and can serve as a cancer therapeutic target, which is the main objective of this study. Here, we show that stroma of human prostate and colon cancer express higher levels of TIMP-1 compared to their normal counterparts and increased expression of TIMP-1 promotes in vivo growth of both cancer types. We demonstrate for the first time that increased TIMP-1 expression stimulates accumulation of cancer associated fibroblasts (CAFs) within prostate and colon cancer tissues and that TIMP-1 enhances prostate CAF proliferation and migration in vitro and promotes ERK1/2 kinase activation in these CAF cells. Our results establish the novel promotive effects of TIMP-1 on cancer progression and on accumulation of CAFs that in turn provides a pro-tumor microenvironment. Together, these results establish the potential of TIMP-1 as a novel target for cancer therapy and the mechanism underlying the pro-tumor activity of TIMP-1.
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