ArticleCancer biology & therapy2011
Decreased zinc and downregulation of ZIP3 zinc uptake transporter in the development of pancreatic adenocarcinoma.
Article in Cancer biology & therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 70 citations in OpenAlex.
- Survival of Laryngeal Cancer Patients Depending on Zinc Serum Level and Oxidative Stress Genotypes.Biomolecules · 2021Trial
- Review
- ZIP1-dependent lymphatic adaptations facilitate lymph node metastasis of pancreatic cancer.International journal of biological sciences · 2026Article
- Zinc-Mediated Defenses Against Toxic Heavy Metals and Metalloids: Mechanisms, Immunomodulation, and Therapeutic Relevance.International journal of molecular sciences · 2025Review
- Zinc Oxide Nanoparticles and Cancer Chemotherapy: Helpful Tools for Enhancing Chemo-sensitivity and Reducing Side Effects?Biological trace element research · 2024Review
- Targeting Solute Carrier Transporters (SLCs) as a Therapeutic Target in Different Cancers.Diseases (Basel, Switzerland) · 2024Review
- Cellular zinc metabolism and zinc signaling: from biological functions to diseases and therapeutic targets.Signal transduction and targeted therapy · 2024Review
- Research progress on the molecular structure, function, and application in tumor therapy of zinc transporter ZIP4.International journal of biological sciences · 2024Review
- Zinc: From Biological Functions to Therapeutic Potential.International journal of molecular sciences · 2023Review
- Construction of a prognostic model for colorectal adenocarcinoma based on Zn transport-related genes identified by single-cell sequencing and weighted co-expression network analysis.Frontiers in oncology · 2023Article
- Structural informatic study of determined and AlphaFold2 predicted molecular structures of 13 human solute carrier transporters and their water-soluble QTY variants.Scientific reports · 2022Article
- Zinc ions negatively regulate proapoptotic signaling in cells expressing oncogenic mutant Ras.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2022Article
- The Transcription ofFrontiers in immunology · 2022Article
- Zinc transporter SLC39A13/ZIP13 facilitates the metastasis of human ovarian cancer cells via activating Src/FAK signaling pathway.Journal of experimental & clinical cancer research : CR · 2021Article
- Emerging roles of the solute carrier family in pancreatic cancer.Clinical and translational medicine · 2021Review
- Zinc dysregulation in cancers and its potential as a therapeutic target.Cancer biology & medicine · 2020Review
- Zinc: The Wonder Drug for the Treatment of Carcinomas.Acta scientific cancer biology · 2020Article
- Growth Modulatory Role of Zinc in Prostate Cancer and Application to Cancer Therapeutics.International journal of molecular sciences · 2020Review
- Transcription Factor RREB1: from Target Genes towards Biological Functions.International journal of biological sciences · 2020Review
- Role of ion channels in gastrointestinal cancer.World journal of gastroenterology · 2019Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Pancreatic adenocarcinoma is an untreatable deadly cancer. The factors involved in its early development remain unknown; which contributes to the absence of biomarkers for early detection of malignancy or at-risk subjects, and the absence of efficacious therapeutic agents. Because zinc changes are implicated in some cancers, we determined if it might be involved in the development of pancreatic adenocarcinoma. With in situ Dithizone and Zinquin staining of normal pancreas and adenocarcinoma tissue sections, we show for the first time, a consistent major loss of zinc in ductal and acinar epithelium in adenocarcinoma compared to the normal epithelium. This decrease in zinc is evident in well-differentiated through poorly-differentiated stages of malignancy. Immunohistochemistry identified ZIP3 as the basilar membrane zinc uptake transporter in normal ductal/acinar epithelium; and that the transporter is absent in adenocarcinoma. In situ Rt-PCR revealed that ZIP3 gene expression is silenced in adenocarcinoma. The ZIP3 down regulation accompanied the loss of zinc in early and progressing malignancy. RREB1 transcription factor was down regulated along with ZIP3; and might be involved in the silencing of ZIP3 expression. Zinc treatment was cytotoxic to malignant Panc1 cells. The combination of concurrent zinc, ZIP3, and RREB-1 changes represent early events in the development of adenocarcinoma; and suggest that zinc might be a tumor suppressor of pancreatic cancer. This report provides the clinical foundation for further mechanistic studies that will provide important insight into pancreatic carcinogenesis, and can lead to the development of effective early biomarkers and effective therapeutic agents for pancreatic cancer.
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Registered trials
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