ArticleInternational journal of biological sciences2014
ZIP4, a novel determinant of tumor invasion in hepatocellular carcinoma, contributes to tumor recurrence after liver transplantation.
Article in International journal of biological sciences, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Review
- Prognostic and Predictive Significance of Cancer Stem Cell Markers (ZIP-4 and ALDH1A1) in Ovarian Serous Carcinoma Patients: An Immunohistochemical Study.Asian Pacific journal of cancer prevention : APJCP · 2026Article
- Unraveling the role of the solute carrier family in hepatocellular carcinoma: mechanisms and therapeutic prospects.Cancer cell international · 2025Review
- Zinc Transporters of the LIV-1 Subfamily in Various Cancers: Molecular Insights and Research Priorities for Saudi Arabia.International journal of molecular sciences · 2025Review
- SLC30 (ZnT) and SLC39 (ZIP) zinc transporter families: from gatekeepers of zinc homeostasis to promoters of tumorigenesis and targets for clinical therapy.Frontiers in immunology · 2025Review
- ZIP4 inhibits Ephrin-B1 ubiquitination, activating Wnt5A/JNK/ZEB1 to promote liver cancer metastasis.Genes & diseases · 2024Article
- Emerging Perspectives in Zinc Transporter Research in Prostate Cancer: An Updated Review.Nutrients · 2024Review
- A prognostic and immune related risk model based on zinc homeostasis in hepatocellular carcinoma.iScience · 2024Article
- Cellular zinc metabolism and zinc signaling: from biological functions to diseases and therapeutic targets.Signal transduction and targeted therapy · 2024Review
- ZIP4: a promising early diagnostic and therapeutic targets for pancreatic cancer.American journal of cancer research · 2024Review
- Research progress on the molecular structure, function, and application in tumor therapy of zinc transporter ZIP4.International journal of biological sciences · 2024Review
- The Transcription ofFrontiers in immunology · 2022Article
- Zinc Favors Triple-Negative Breast Cancer's Microenvironment Modulation and Cell Plasticity.International journal of molecular sciences · 2021Article
- Article
- Article
- The role of zinc transporter proteins as predictive and prognostic biomarkers of hepatocellular cancer.PeerJ · 2021Article
- Article
- The Role of Zinc and Copper in Gynecological Malignancies.Nutrients · 2020Review
- Serum zinc level and tissue ZIP4 expression are related to the prognosis of patients with stages I-III colon cancer.Translational cancer research · 2020Article
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13 authors.
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No grant is acknowledged in the PubMed record.
Abstract
background and purposeRecently, evidence that Zinc transporter ZRT/IRT-like protein 4 (ZIP4) is involved in invasiveness and apoptosis has emerged in pancreatic cancer and prostate cancer. Our aim was to assess the role of ZIP4 in invasiveness, migration and apoptosis of hepatocellular carcinoma (HCC). The prognostic value of ZIP4 in HCC after liver transplantation was evaluated.
methodsThe role of ZIP4 in HCC was investigated by overexpressing ZIP4 in BEL7402 and HepG2 cells and inhibiting ZIP4 in HuH-7 and HepG2 cells, using overexpression and shRNA plasmids in vitro studies. Immunohistochemical analysis was used to evaluate ZIP4 expression in HCC tissues from 60 patients undergoing liver transplantation, 36 cirrhotic tissue samples, and 6 normal tissue samples. Prognostic significance was assessed using the Kaplan-Meier method and the log-rank test.
resultsSpecific suppression of ZIP4 reduced cell migration and invasiveness, whereas ZIP4 overexpression caused increases in cell migration and invasiveness. Furthermore, overexpression of ZIP4 resulted in increased expression of pro-metastatic genes (MMP-2, MMP-9) and decreased expression of pro-apoptotic genes (caspase-3, caspase-9, Bax). In contrast, suppression of ZIP4 resulted in an opposite effect. ZIP4 was more highly expressed in tumor tissues than non-tumor tissues (P < 0.0001). ZIP4 expression was significantly associated with tumor recurrence (P = 0.002), tumor node metastasis stage (P = 0.044), Child-Turcotte-Pugh score (P = 0.042), and tumor size (P = 0.022). Univariate analysis showed that ZIP4 expression was significantly associated with overall survival (P = 0.020) and tumor-free survival (P = 0.049). Multivariate analysis revealed that ZIP4 was an independent predictor of overall survival (P = 0.037) after liver transplantation.
conclusionsZIP4 could promote migration, invasiveness, and suppress apoptosis in hepatocellular carcinoma, and represent a novel predictor of poor prognosis and therapeutic target for patients with HCC who undergo liver transplantation.
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