ArticleOncotarget2015
TIMP-1 activated carcinoma-associated fibroblasts inhibit tumor apoptosis by activating SDF1/CXCR4 signaling in hepatocellular carcinoma.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 90 citations in OpenAlex.
- The Dual Roles of TIMP-1 in Cancer: From Protease Inhibition to Cytokine Signaling.Molecular biology reports · 2026Review
- Signalling pathways in hepatocellular carcinoma (HCC) metastasis and invasion: Molecular mechanisms and therapeutic implications.Biochemistry and biophysics reports · 2026Review
- Review
- Hotspots and frontiers of the relationship between hepatocellular carcinoma and cancer-associated fibroblasts: a bibliometric analysis and review.Discover oncology · 2025Article
- Fibroblasts Are the Primary Contributors to a Disrupted Micro-Environment in End-Stage Pediatric Hypertrophic Cardiomyopathy.Circulation. Genomic and precision medicine · 2025Article
- Mechanisms of drug resistance in hepatocellular carcinoma.Biological procedures online · 2025Review
- Tissue inhibitor of metalloproteinase 1 as a biomarker of venous invasion in pancreatic ductal adenocarcinoma.American journal of cancer research · 2025Article
- Integrative genomics unveils basement membrane-related diagnostic markers and therapeutic targets in esophageal squamous cell carcinoma.Biology direct · 2024Article
- Unraveling the underlying pathogenic factors driving nonalcoholic steatohepatitis and hepatocellular carcinoma: an in-depth analysis of prognostically relevant gene signatures in hepatocellular carcinoma.Journal of translational medicine · 2024Article
- Function and biomedical implications of exosomal microRNAs delivered by parenchymal and nonparenchymal cells in hepatocellular carcinoma.World journal of gastroenterology · 2023Review
- Combination of Phenethyl Isothiocyanate and Dasatinib Inhibits Hepatocellular Carcinoma Metastatic Potential through FAK/STAT3/Cadherin Signalling and Reduction of VEGF Secretion.Pharmaceutics · 2023Article
- Novel CAF-identifiers via transcriptomic and protein level analysis in HNSC patients.Scientific reports · 2023Article
- A Paradigm Shift in Primary Liver Cancer Therapy Utilizing Genomics, Molecular Biomarkers, and Artificial Intelligence.Cancers · 2023Review
- Non-Parenchymal Cells and the Extracellular Matrix in Hepatocellular Carcinoma in Non-Alcoholic Fatty Liver Disease.Cancers · 2023Review
- Emerging Role of Cancer-Associated Fibroblasts in Progression and Treatment of Hepatocellular Carcinoma.International journal of molecular sciences · 2023Review
- CAFs-derived SCUBE1 promotes malignancy and stemness through the Shh/Gli1 pathway in hepatocellular carcinoma.Journal of translational medicine · 2022Article
- Advances of cancer-associated fibroblasts in liver cancer.Biomarker research · 2022Review
- The tumor microenvironment of hepatocellular carcinoma and its targeting strategy by CAR-T cell immunotherapy.Frontiers in endocrinology · 2022Review
- Review
- HepatoScore-14: Measures of Biological Heterogeneity Significantly Improve Prediction of Hepatocellular Carcinoma Risk.Hepatology (Baltimore, Md.) · 2021Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tissue inhibitor of metalloproteinase 1 (TIMP-1) is an endogenous inhibitor for MMPs that regulates the remodeling and turnover of the ECM during normal development and pathological conditions. Intriguingly, recent studies have shown that TIMP-1 plays a dual role in cancer progression. In this study, we found that TIMP-1 expression in HCC tissues is associated with advanced TNM stage, intrahepatic metastasis, portal vein invasion, and vasculature invasion. Notably, TIMP-1 expression in HCC tissue is significantly related to worse overall survival for patients with HCC after liver resection. Ectopic TIMP1 expression promoted the growth of HCC xenografts in nude mice. Both co-culture with Huh7 cells with a high level of TIMP-1 and TIMP1 treatment resulted in up-regulation of hallmarks of carcinoma-associated fibroblasts (CAFs) and accelerated cell proliferation, migration and invasion in immortalized liver fibroblasts (LFs) isolated from human normal liver tissue. By co-culture with CAFs, SDF-1/CXCR4/PI3K/AKT signaling was activated and apoptosis was markedly repressed with an increased Bcl-2/BAX ratio in Huh7 cells. Taken together, our observations suggest that TIMP-1 induces the trans-differentiation of LFs into CAFs, suppresses apoptosis via SDF-1/CXCR4/PI3K/AKT signaling and then promotes HCC progression. This protein may be a potential prognostic biomarker and therapeutic target for HCC.
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