Defining the human copper proteome and analysis of its expression variation in cancers
| Autor: | Juan Carlos Fierro-González, Amir Feizi, Olle Stål, Emanuele Celauro, Camilla Hildesjö, Pernilla Wittung-Stafshede, Stéphanie Blockhuys |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Proteome Biophysics Breast Neoplasms Computational biology Biology Bioinformatics Biochemistry Metastasis Biomaterials 03 medical and health sciences Metalloproteins medicine Humans Transcription factor Gene Retrospective Studies Regulation of gene expression Cancer och onkologi Gene Expression Profiling Metals and Alloys RNA medicine.disease Gene Expression Regulation Neoplastic Gene expression profiling 030104 developmental biology Chemistry (miscellaneous) Cancer and Oncology Female Functional genomics Copper |
| Zdroj: | Europe PubMed Central |
| ISSN: | 1756-591X 1756-5901 |
| DOI: | 10.1039/c6mt00202a |
| Popis: | 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 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. Funding agencies: Swedish Society for Medical Research; Folke and Marianne Edler Research Fund; Lars Hierta Memorial Foundation; Knut and Alice Wallenberg Foundation; Swedish Research Council; Chalmers Foundation; NBIS (National Bioinformatics Infrastructure Sweden) |
| Databáze: | OpenAIRE |
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