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Issue 2, 2017
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Defining the human copper proteome and analysis of its expression variation in cancers

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Abstract

Copper (Cu) is essential for living organisms, and acts as a cofactor in many metabolic enzymes. To avoid the toxicity of free Cu, organisms have specific transport systems that ‘chaperone’ the metal to targets. Cancer progression is associated with increased cellular Cu concentrations, whereby proliferative immortality, angiogenesis and metastasis are cancer hallmarks with defined requirements for Cu. The aim of this study is to gather all known Cu-binding proteins and reveal their putative involvement in cancers using the available database resources of RNA transcript levels. Using the Uniprot.org database along with manual curation, we identified a total of 54 Cu-binding proteins (named the human Cu proteome). Next, we retrieved RNA expression levels in cancer versus normal tissues from the TCGA database for the human Cu proteome in 18 cancer types, and noted an intricate pattern of up- and downregulation of the genes in different cancers. Hierarchical clustering in combination with bioinformatics and functional genomics analyses allowed for the prediction of cancer-related Cu-binding proteins; these were specifically inspected for the breast cancer data. Finally, for the Cu chaperone ATOX1, which is the only Cu-binding protein proposed to have transcription factor activities, we validated its predicted over-expression in patient breast cancer tissue at the protein level. This collection of Cu-binding proteins, with RNA expression patterns in different cancers, will serve as an excellent resource for mechanistic–molecular studies of Cu-dependent processes in cancer.

Graphical abstract: Defining the human copper proteome and analysis of its expression variation in cancers

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Supplementary files

Article information


Submitted
17 Sep 2016
Accepted
01 Dec 2016
First published
01 Dec 2016

This article is Open Access

Metallomics, 2017,9, 112-123
Article type
Paper

Defining the human copper proteome and analysis of its expression variation in cancers

S. Blockhuys, E. Celauro, C. Hildesjö, A. Feizi, O. Stål, J. C. Fierro-González and P. Wittung-Stafshede, Metallomics, 2017, 9, 112
DOI: 10.1039/C6MT00202A

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