ArticleOncogene2016
Regulation of a TGF-β1-CD147 self-sustaining network in the differentiation plasticity of hepatocellular carcinoma cells.
Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 41 citations in OpenAlex.
- Inhibition of TGF-β1/Smad signaling reverses the dedifferentiated phenotype of thyroid cancer cells in three-dimensional culture.Journal of endocrinological investigation · 2026Article
- TGFβ1 Activates Lnc-APUE to Promote Tumor Metastasis via the Alu Element-Driven STAU1-Mediated Decay of CDH1 mRNA.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Modulation of Network Plasticity Opens Novel Therapeutic Possibilities in Cancer, Diabetes, and Neurodegeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- The Anti-EMMPRIN Monoclonal Antibody hMR18-mAb Induces Tumor Dormancy and Inhibits the EMT Process in Human Carcinoma Cell Lines Co-Cultured with Macrophages.Biomedicines · 2025Article
- CD147 at the crossroads of glycoprotein networks, metabolic reprogramming, and metastatic progression.Frontiers in immunology · 2025Review
- Serum EMMPRIN/CD147 promotes the lung pre-metastatic niche in a D2A1 mammary carcinoma mouse model.Frontiers in immunology · 2025Article
- Signaling pathways in liver cancer: pathogenesis and targeted therapy.Molecular biomedicine · 2024Review
- EMMPRIN promotes spheroid organization and metastatic formation: comparison between monolayers and spheroids of CT26 colon carcinoma cells.Frontiers in immunology · 2024Article
- Article
- N-glycosylation-mediated CD147 accumulation induces cardiac fibrosis in the diabetic heart through ALK5 activation.International journal of biological sciences · 2023Article
- CD147 contributes to SARS-CoV-2-induced pulmonary fibrosis.Signal transduction and targeted therapy · 2022Article
- Rs6757 in microRNA-3976 binding site of CD147 confers risk of hepatocellular carcinoma in South Chinese population.World journal of surgical oncology · 2022Article
- The Multiple Roles of CD147 in the Development and Progression of Oral Squamous Cell Carcinoma: An Overview.International journal of molecular sciences · 2022Review
- Active demethylation upregulates CD147 expression promoting non-small cell lung cancer invasion and metastasis.Oncogene · 2022Article
- Novel Cellular Therapies for Hepatocellular Carcinoma.Cancers · 2022Review
- Identifying In Vitro Cultured Human Hepatocytes Markers with Machine Learning Methods Based on Single-Cell RNA-Seq Data.Frontiers in bioengineering and biotechnology · 2022Article
- Mini-Review: Can the Metastatic Cascade Be Inhibited by Targeting CD147/EMMPRIN to Prevent Tumor Recurrence?Frontiers in immunology · 2022Review
- Hepatocellular Carcinoma Differentiation: Research Progress in Mechanism and Treatment.Frontiers in oncology · 2021Review
- Cancer stemness in hepatocellular carcinoma: mechanisms and translational potential.British journal of cancer · 2020Review
- Dedifferentiation of hepatocellular carcinoma: molecular mechanisms and therapeutic implications.American journal of translational research · 2020Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cellular plasticity has an important role in the progression of hepatocellular carcinoma (HCC). In this study, the involvement of a TGF-β1-CD147 self-sustaining network in the regulation of the dedifferentiation progress was fully explored in HCC cell lines, hepatocyte-specific basigin/CD147-knockout mice and human HCC tissues. We demonstrated that TGF-β1 stimulation upregulated CD147 expression and mediated the dedifferentiation of HCC cells, whereas all-trans-retinoic acid induced the downregulation of CD147 and promoted differentiation in HCC cells. Overexpression of CD147 induced the dedifferentiation and enhanced the malignancy of HCC cells, and increased the transcriptional expression of TGF-β1 by activating β-catenin. CD147-induced matrix metalloproteinase (MMP) production activated pro-TGF-β1. The activated TGF-β1 signaling subsequently repressed the HNF4α expression via Smad-Snail1 signaling and enhanced the dedifferentiation progress. Hepatocyte-specific basigin/CD147-knockout mice decreased the susceptibility to N-nitrosodiethylamine-induced tumorigenesis by suppressing TGF-β1-CD147 signaling and inhibiting dedifferentiation in hepatocytes during tumor progression. CD147 was positively correlated with TGF-β1 and negatively correlated with HNF4α in human HCC tissues. Positive CD147 staining and lower HNF4α levels in tumor tissues were significantly associated with poor survival of patients with HCC. The overexpression of HNF4α and Smad7 and the deletion of CD147 by lentiviral vectors jointly reprogrammed the expression profile of hepatocyte markers and attenuated malignant properties including proliferation, cell survival and tumor growth of HCC cells. Our results highlight the important role of the TGF-β1-CD147 self-sustaining network in driving HCC development by regulating differentiation plasticity, which provides a strong basis for further investigations of the differentiation therapy of HCC targeting TGF-β1 and CD147.
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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.