Defining the human copper proteome and analysis of its expression variation in cancers.
Artikel i vetenskaplig tidskrift, 2017

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.

Författare

Stephanie Blockhuys

Chalmers, Biologi och bioteknik, Kemisk biologi

Emanuele Celauro

Chalmers, Biologi och bioteknik, Kemisk biologi

C. Hildesjo

County Council of Östergötland

Linköpings universitet

Amir Feizi

Chalmers, Biologi och bioteknik, Systembiologi

O Stål

Linköpings universitet

Juan Carlos Fierro González

Chalmers, Biologi och bioteknik, Kemisk biologi

Pernilla Wittung Stafshede

Chalmers, Biologi och bioteknik, Kemisk biologi

Metallomics

1756-5901 (ISSN) 1756-591X (eISSN)

Vol. 9 112-123

Ämneskategorier

Cellbiologi

Biokemi och molekylärbiologi

Biologiska vetenskaper

Biofysik

Bioinformatik och systembiologi

DOI

10.1039/c6mt00202a

PubMed

27942658