ArticleScientific reports2017
Up-regulation of chemokine receptor CCR4 is associated with Human Hepatocellular Carcinoma malignant behavior.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 63 citations in OpenAlex.
- Mogamulizumab in Combination with Nivolumab in a Phase I/II Study of Patients with Locally Advanced or Metastatic Solid Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- Regulatory T Cells in Hepatocellular Carcinoma: Spatial Niches, Biomarkers, and Clinical Implications.International journal of molecular sciences · 2026Review
- CCR-CCL axes as key upstream influencers of pancreatic ductal adenocarcinoma: CCR2-CCL2, CCR5-CCL5, CCR4-CCL17/22, CCR6-CCL20, CCR7-CCL19/21.Frontiers in immunology · 2026Review
- Chemokine Receptor Profiles as Predictors of Survival and Early Progression in Follicular Lymphoma.EJHaem · 2025Article
- M2-like Macrophages-derived CCL17 Promotes Esophageal Squamous Cell Carcinoma Metastasis and Stemness via Activating CCR4-mediated ERK/PD-L1 Pathway.Current molecular medicine · 2025Article
- CC Chemokine Family Members' Modulation as a Novel Approach for Treating Central Nervous System and Peripheral Nervous System Injury-A Review of Clinical and Experimental Findings.International journal of molecular sciences · 2024Review
- Dynamic changes in immune cell populations by AXL kinase targeting diminish liver inflammation and fibrosis in experimental MASH.Frontiers in immunology · 2024Article
- Chemokines in the tumor microenvironment: implications for lung cancer and immunotherapy.Frontiers in immunology · 2024Review
- Key oncogenic signaling pathways affecting tumor-infiltrating lymphocytes infiltration in hepatocellular carcinoma: basic principles and recent advances.Frontiers in immunology · 2024Review
- CCR4 Blockade Diminishes Intratumoral Macrophage Recruitment and Augments Survival of Syngeneic Pancreatic Cancer-Bearing Mice.Biomedicines · 2023Article
- Blockade of CCR4 breaks immune tolerance in chronic hepatitis B patients by modulating regulatory pathways.Journal of translational medicine · 2023Article
- Key Members of the CmPn as Biomarkers Distinguish Histological and Immune Subtypes of Hepatic Cancers.Diagnostics (Basel, Switzerland) · 2023Article
- Novel Theranostic Approaches Targeting CCR4-Receptor, Current Status and Translational Prospectives: A Systematic Review.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Friend or Foe - Tc17 cell generation and current evidence for their importance in human disease.Discovery immunology · 2023Review
- CCL17 and CCL22 chemokines are upregulated in human obesity and play a role in vascular dysfunction.Frontiers in endocrinology · 2023Article
- CC Chemokine Receptor 4 (CCR4) as a Possible New Target for Therapy.International journal of molecular sciences · 2022Review
- Chemokine clouding and liver cancer heterogeneity: Does it impact clinical outcomes?Seminars in cancer biology · 2022Review
- Targeting CCL2-CCR4 axis suppress cell migration of head and neck squamous cell carcinoma.Cell death & disease · 2022Article
- The Evasion Mechanisms of Cancer Immunity and Drug Intervention in the Tumor Microenvironment.Frontiers in pharmacology · 2022Review
- ETV1 Positively Correlated With Immune Infiltration and Poor Clinical Prognosis in Colorectal Cancer.Frontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Studies indicate that the chemokine receptor is responsible for poor prognosis of hepatocellular carcinoma (HCC) patients. In this study, we initially demonstrated that CCR4 is overexpressed in HCC specimens, and its elevation in HCC tissues positively correlates with tumor capsule breakthrough and vascular invasion. Although overexpression of CCR4 failed to influent proliferation of HCC cells in vitro apparently, the prominent acceleration on HCC tumor growth in vivo was remarkable. The underlying mechanism may be involved in neovascularization. Interestingly, different from effect on proliferation, CCR4 overexpression could trigger HCC metastasis both in vitro and in vivo also induced HCC cell epithelial-mesenchymal transition (EMT) as well. Then we identified matrix metalloproteinase 2 (MMP2) as a direct target of CCR4 which plays an important role in CCR4-mediated HCC cell invasion, which was up-regulated by ERK/AKT signaling. Positive correlation between CCR4 and MMP2 expression was also observed in HCC tissues. In conclusion, our study suggested that chemokine receptor CCR4 promotes HCC malignancy and facilitated HCC cell metastases via ERK/AKT/MMP2 pathway. These findings suggest that CCR4 may be a potential new diagnostic and prognostic marker in HCC, and targeting CCR4 may be a potential therapeutic option for blocking HCC metastasis.
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Registered trials
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