ArticleProceedings of the National Academy of Sciences of the United States of America2007
Aberrant expression of zinc transporter ZIP4 (SLC39A4) significantly contributes to human pancreatic cancer pathogenesis and progression.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 160 papers.
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Who cites it
160 citing papers in PubMed, 247 citations in OpenAlex.
- Phytochemicals as Multitarget Therapeutics in Pancreatic Cancer: Mechanisms, Clinical Evidence, and Translational Challenges.Phytotherapy research : PTR · 2026Review
- Molecular Imaging of In Vivo Zinc Distribution Using Nuclear and Magnetic Resonance Imaging.Chemical & biomedical imaging · 2026Review
- Article
- Zinc-induced exposure of an LxL motif drives clathrin-mediated endocytosis of the zinc transceptor ZIP4.The Journal of biological chemistry · 2026Article
- Trace Elements in the Pancreas: From Physiological Homeostasis to the Pathogenesis of Diabetes, Pancreatitis, and Cancer-A Review.Life (Basel, Switzerland) · 2026Review
- YTHDF1/SLC39A4 signaling axis promotes gastric cancer cell proliferation by suppressing cuproptosis ex vivo and in vitro.Cancer gene therapy · 2026Article
- Review
- ZIP1-dependent lymphatic adaptations facilitate lymph node metastasis of pancreatic cancer.International journal of biological sciences · 2026Article
- Probing of substrate binding-induced conformational switch of a ZIP metal transporter using sandwich ELISA.Scientific reports · 2025Article
- Molecular MRI of Dysregulated Zinc Secretion Detects Pancreatic Ductal Adenocarcinoma and Response to KRASG12D Inhibitor Treatment.Cancer research · 2025Article
- SOX4-ZIP14-zinc metabolism mediates oncogenesis and suppresses T cell immunity in nasopharyngeal carcinoma.Cell reports. Medicine · 2025Article
- Zinc Transporters of the LIV-1 Subfamily in Various Cancers: Molecular Insights and Research Priorities for Saudi Arabia.International journal of molecular sciences · 2025Review
- A zinc transporter drives glioblastoma progression via extracellular vesicles-reprogrammed microglial plasticity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Molecular insights into substrate translocation in an elevator-type metal transporter.Nature communications · 2024Article
- Zinc transporter ZnT5 is associated with epithelial mesenchymal transition via SMAD1 in breast cancer.International journal of experimental pathology · 2024Article
- Evolution, classification, and mechanisms of transport, activity regulation, and substrate specificity of ZIP metal transporters.Critical reviews in biochemistry and molecular biology · 2024Review
- 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
- Emerging Perspectives in Zinc Transporter Research in Prostate Cancer: An Updated Review.Nutrients · 2024Review
- The crosstalk between macrophages and cancer cells potentiates pancreatic cancer cachexia.Cancer cell · 2024Article
100 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 4 institutions in 1 country.
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Abstract
Zinc is an essential trace element and catalytic/structural component used by many metalloenzymes and transcription factors. Recent studies indicate a possible correlation of zinc levels with the cancer risk; however, the exact role of zinc and zinc transporters in cancer progression is unknown. We have observed that a zinc transporter, ZIP4 (SLC39A4), was substantially overexpressed in 16 of 17 (94%) clinical pancreatic adenocarcinoma specimens compared with the surrounding normal tissues, and ZIP4 mRNA expression was significantly higher in human pancreatic cancer cells than human pancreatic ductal epithelium (HPDE) cells. This indicates that aberrant ZIP4 up-regulation may contribute to the pancreatic cancer pathogenesis and progression. We studied the effects of ZIP4 overexpression in pancreatic cancer cell proliferation in vitro and pancreatic cancer progression in vivo. We found that forced expression of ZIP4 increased intracellular zinc levels, increased cell proliferation by 2-fold in vitro, and significantly increased tumor volume by 13-fold in the nude mice model with s.c. xenograft compared with the control cells. In the orthotopic nude mice model, overexpression of ZIP4 not only increased the primary tumor weight (7.2-fold), it also increased the peritoneal dissemination and ascites incidence. Moreover, increased cell proliferation and higher zinc content were also observed in the tumor tissues that overexpressed ZIP4. These data reveal an important outcome of aberrant ZIP4 expression in contributing to pancreatic cancer pathogenesis and progression. It may suggest a therapeutic strategy whereby ZIP4 is targeted to control pancreatic cancer growth.
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