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Role of ZIP8 in regulating cell morphology and NF-κB/Snail2 signaling


ZIP8 is a recently identified membrane transporter which facilitates uptake of many substrates including both essential and toxic divalent metals (e.g. zinc, manganese, iron, cadmium) and inorganic selenium. Many ZIP8 regulated downstream signals and pathways remain to be elucidated. In this study, we investigated ZIP8 regulatory roles in downstream regulated targets in ZIP8-gain and loss cells and in ZIP8 overexpressed lung. Our results showed that overexpression of ZIP8 in mouse fibroblast cells (MEF) induced an epithelial to mesenchymal transition (EMT)-like morphological change and re-organization of filament actin (F-actin), along with increased cells proliferation and migration rate. In ZIP8 knockout chronic myelogenous leukemia HAP1 cells, significant clonal morphological change was observed. In ZIP8 overexpressed lung, F-actin was aberrantly enriched around tracheal branch. In these ZIP8 gain and loss of cell lines and ZIP8 transgenic lung, we identified two relevant signaling molecules NF-κB and Snail2, which activation is dependent on ZIP8 level. They were significantly upregulated in ZIP8 overexpressed cells and lung. Expression of NF-κB and Snail2 targets, COL1A2 and E-cadherin, were also correspondingly elevated. Taking together, our results suggest that ZIP8 is new regulator for cell morphology and cytoskeleton which involve NF-κB and Snail2 signaling.

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Publication details

The article was received on 08 Apr 2018, accepted on 05 Jun 2018 and first published on 05 Jun 2018

Article type: Paper
DOI: 10.1039/C8MT00079D
Citation: Metallomics, 2018, Accepted Manuscript
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    Role of ZIP8 in regulating cell morphology and NF-κB/Snail2 signaling

    X. Geng, L. Liu, A. Banes-Berceli, Z. Yang, P. Kang, J. Shen, K. Tsai and Z. Liu, Metallomics, 2018, Accepted Manuscript , DOI: 10.1039/C8MT00079D

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