Zinc transporters and dysregulated channels in cancers

Zui Pan, Sangyong Choi, Halima Ouadid-Ahidouch, Jin-Ming Yang, John H Beattie, Irina Korichneva

Research output: Contribution to journalArticlepeer-review

79 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)623-643
Number of pages21
JournalFrontiers in Bioscience
Volume22
DOIs
Publication statusPublished - 1 Jan 2017

Bibliographical note

The authors would like to acknowledge financial support from NIH-NCI (R01-CA185055), UMDNJ Foundation (62-09) and Pelotonia to ZP, the Rural and Environment Science and Analytical Services of the Scottish Government to JHB, the Region Hauts-de-France to IK and the contribution of the COST Action TD1304.

Item is deposited in PMC in compliance with REF policy.

Keywords

  • Zn Homeostasis
  • ZnT
  • ZIP
  • TRP channels
  • store-operated Ca2+
  • entry
  • Orai channels
  • STIM
  • prostate cancer
  • breast cancer
  • esophageal cancer
  • review

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