ArticlePloS one2010
Zip4 (Slc39a4) expression is activated in hepatocellular carcinomas and functions to repress apoptosis, enhance cell cycle and increase migration.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 87 citations in OpenAlex.
- YTHDF1/SLC39A4 signaling axis promotes gastric cancer cell proliferation by suppressing cuproptosis ex vivo and in vitro.Cancer gene therapy · 2026Article
- Review
- Probing of substrate binding-induced conformational switch of a ZIP metal transporter using sandwich ELISA.Scientific reports · 2025Article
- 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
- Molecular insights into substrate translocation in an elevator-type metal transporter.Nature communications · 2024Article
- Molecular insights into substrate translocation in an elevator-type metal transporter.bioRxiv : the preprint server for biology · 2024Article
- Determination of metal ion transport rate of human ZIP4 using stable zinc isotopes.The Journal of biological chemistry · 2024Article
- Current Trends on the Involvement of Zinc, Copper, and Selenium in the Process of Hepatocarcinogenesis.Nutrients · 2024Review
- Article
- Review
- Article
- Structural insights into the elevator-type transport mechanism of a bacterial ZIP metal transporter.Nature communications · 2023Article
- Review
- The zinc transporter ZIP12 regulates monocrotaline-induced proliferation and migration of pulmonary arterial smooth muscle cells via the AKT/ERK signaling pathways.BMC pulmonary medicine · 2022Article
- RASSF1A independence and early galectin-1 upregulation in PIK3CA-induced hepatocarcinogenesis: new therapeutic venues.Molecular oncology · 2022Article
- Article
- Systemic characterization of the SLC family genes reveals SLC26A6 as a novel oncogene in hepatocellular carcinoma.Translational cancer research · 2021Article
- The role of labile ZnMolecular and cellular biochemistry · 2021Review
- Knockdown of SLC39A4 Expression Inhibits the Proliferation and Motility of Gallbladder Cancer Cells and Tumor Formation in Nude Mice.Cancer management and research · 2021Article
Corrections and comments
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Authors and funding
9 authors at 7 institutions in 2 countries.
Funding
Abstract
backgroundThe zinc transporter ZIP4 (Slc39a4) is important for proper mammalian development and is an essential gene in mice. Recent studies suggest that this gene may also play a role in pancreatic cancer. METHODS/PRINCIPAL
findingsHerein, we present evidence that this essential zinc transporter is expressed in hepatocellular carcinomas. Zip4 mRNA and protein were dramatically elevated in hepatocytes in the majority of human hepatocellular carcinomas relative to noncancerous surrounding tissues, as well as in hepatocytes in hepatocellular carcinomas occurring in farnesoid X receptor-knockout mice. Interestingly, meta-analysis of microarray data in the Geo and Oncomine databases suggests that Zip4 mRNA may also be elevated in many types of cancer. Potential mechanisms of action of ZIP4 were examined in cultured cell lines. RNAi knockdown of Zip4 in mouse Hepa cells significantly increased apoptosis and modestly slowed progression from G(0)/G(1) to S phase when cells were released from hydroxyurea block into zinc-deficient medium. Cell migration assays revealed that RNAi knockdown of Zip4 in Hepa cells depressed in vitro migration whereas forced over-expression in Hepa cells and MCF-7 cells enhanced in vitro migration.
conclusionsZIP4 may play a role in the acquisition of zinc by hepatocellular carcinomas, and potentially many different cancerous cell-types, leading to repressed apoptosis, enhanced growth rate and enhanced invasive behavior.
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