Zinc transporters and dysregulated channels in cancers.
As a nutritionally essential metal ion, zinc (Zn) not only constitutes a structural element for more than 3000 proteins but also plays important regulatory functions in cellular signal transduction. Zn homeostasis is tightly controlled by regulating the flux of Zn across cell membranes through specific transporters, i.e. ZnT and ZIP family proteins. Zn deficiency and malfunction of Zn transporters have been associated with many chronic diseases including cancer. However, the mechanisms underlying Zn regulatory functions in cellular signaling and their impact on the pathogenesis and progression of cancers remain largely unknown. In addition to these acknowledged multifunctions, Zn modulates a wide range of ion channels that in turn may also play an important role in cancer biology. The goal of this review is to propose how zinc deficiency, through modified Zn homeostasis, transporter activity and the putative regulatory function of Zn can influence ion channel activity, and thereby contribute to carcinogenesis and tumorigenesis. This review intends to stimulate interest in, and support for research into the understanding of Zn-modulated channels in cancers, and to search for novel biomarkers facilitating effective clinical stratification of high risk cancer patients as well as improved prevention and therapy in this emerging field.
The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA, zui.pan@osumc.edu.
Zui
Z
Pan
Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
Sangyong
S
Choi
University of Picardie Jules Verne, UFR Sciences, EA 4667, Laboratory of Cell and Molecular Physiology, SFR CAP-SANTE (FED 4231), Amiens, France.
Halima
H
Ouadid-Ahidouch
Department of Pharmacology, College of Medicine, Penn State University, 500 University Drive Hershey, PA 17033, USA.
Jin-Ming
JM
Yang
Rowett Institute of Nutrition and Health, University of Aberdeen, Foresterhill, Bucksburn, Aberdeen AB25 2ZD, Scotland, UK.
John H
JH
Beattie
University of Picardie Jules Verne, UFR Sciences, EA 4667, Laboratory of Cell and Molecular Physiology, SFR CAP-SANTE (FED 4231), Amiens, France.
Irina
I
Korichneva
D000818:Animals; D027682:Cation Transport Proteins / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D007473:Ion Channels / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism*; D000071740:ORAI1 Protein / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism; D050051:Transient Receptor Potential Channels / Q000378:metabolism; D015032:Zinc / Q000172:deficiency / Q000378:metabolism*
D027682:Cation Transport Proteins; D007473:Ion Channels; D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; D015221:Potassium Channels; D050051:Transient Receptor Potential Channels; D015032:Zinc