ArticleOncotarget2017
TGF-β-independent CTGF induction regulates cell adhesion mediated drug resistance by increasing collagen I in HCC.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 45 citations in OpenAlex.
- Proteomic analysis of malignant ascites and its impact on ovarian cancer spheroids.Clinical proteomics · 2026Article
- Navigating the Labyrinth of Hepatocellular Carcinoma: Leveraging AI/ML for Precision Oncology.Oncology research · 2026Review
- Hyaluronidase: structure, mechanism of action, diseases and therapeutic targets.Molecular biomedicine · 2025Review
- The influence of biophysical niche on tumor-associated macrophages in liver cancer.Hepatology communications · 2024Review
- The Spatial Extracellular Proteomic Tumor Microenvironment Distinguishes Molecular Subtypes of Hepatocellular Carcinoma.Journal of proteome research · 2024Article
- Collagen in hepatocellular carcinoma: A novel biomarker and therapeutic target.Hepatology communications · 2024Review
- Scaffold-based 3D cell culture models in cancer research.Journal of biomedical science · 2024Review
- Inhibition of DNMT3B expression in activated hepatic stellate cells overcomes chemoresistance in the tumor microenvironment of hepatocellular carcinoma.Scientific reports · 2024Article
- Exploring the diversity of cancer-associated fibroblasts: insights into mechanisms of drug resistance.Frontiers in cell and developmental biology · 2024Review
- Deciphering the underlying mechanism of liver diseases through utilization of multicellular hepatic spheroid models.BMB reports · 2023Review
- BMP and activin membrane-bound inhibitor regulate connective tissue growth factor controlling mesothelioma cell proliferation.BMC cancer · 2022Article
- Identification of hepatic fibrosis inhibitors through morphometry analysis of a hepatic multicellular spheroids model.Scientific reports · 2021Article
- Analysis and identification of novel biomarkers involved in neuroblastoma via integrated bioinformatics.Investigational new drugs · 2021Article
- CAM-DR: Mechanisms, Roles and Clinical Application in Tumors.Frontiers in cell and developmental biology · 2021Review
- Targeting Liver Cancer Stem Cells: An Alternative Therapeutic Approach for Liver Cancer.Cancers · 2020Review
- Inhibitors of NaScientific reports · 2020Article
- NOTCH3 Overexpression and Posttranscriptional Regulation by miR-150 Were Associated With EGFR-TKI Resistance in Lung Adenocarcinoma.Oncology research · 2019Article
- YAP/TAZ Signaling and Resistance to Cancer Therapy.Trends in cancer · 2019Review
- Extracellular matrix collagen I promotes the tumor progression of residual hepatocellular carcinoma after heat treatment.BMC cancer · 2018Article
- Three Dimensional Mixed-Cell Spheroids Mimic Stroma-Mediated Chemoresistance and Invasive Migration in hepatocellular carcinoma.Neoplasia (New York, N.Y.) · 2018Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocellular carcinoma (HCC) is resistant to conventional chemotherapeutic agents and remains an unmet medical need. Here, we demonstrate a mechanism of cell adhesion-mediated drug resistance using a variety of HCC spheroid models to overcome environment-mediated drug resistance in HCC. We classified spheroids into two groups, tightly compacted and loosely compacted aggregates, based on investigation of dynamics of spheroid formation. Our results show that compactness of HCC spheroids correlated with fibroblast-like characteristics, collagen 1A1 (COL1A1) content, and capacity for chemoresistance. We also showed that ablation of COL1A1 attenuated not only the capacity for compact-spheroid formation, but also chemoresistance. Generally, connective tissue growth factor (CTGF) acts downstream of transforming growth factor (TGF)-β and promotes collagen I fiber deposition in the tumor microenvironment. Importantly, we found that TGF-β-independent CTGF is upregulated and regulates cell adhesion-mediated drug resistance by inducing COL1A1 in tightly compacted HCC spheroids. Furthermore, losartan, which inhibits collagen I synthesis, impaired the compactness of spheroids via disruption of cell-cell contacts and increased the efficacy of anticancer therapeutics in HCC cell line- and HCC patient-derived tumor spheroids. These results strongly suggest functional roles for CTGF-induced collagen I expression in formation of compact spheroids and in evading anticancer therapies in HCC, and suggest that losartan, administered in combination with conventional chemotherapy, might be an effective treatment for liver cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.