“In the light of evolution:” keratins as exceptional tumor biomarkers

PeerJ

article

Işıl Takan¹  Gökhan Karakülah¹  Aikaterini Louka³  Athanasia Pavlopoulou¹ 

[1]Izmir Biomedicine and Genome Center

[2]Izmir International Biomedicine and Genome Institute, Dokuz Eylül University

[3]DNA Damage Laboratory, Department of Physics, School of Applied Mathematical and Physical Sciences, National Technical University of Athens

[4]Section of Cell Biology and Biophysics, Department of Biology, School of Sciences, National and Kapodistrian University of Athens

关键词: Cancer;    Evolution;    Comparative genomics;    Phylogeny;    Data mining;    Interaction network;    Gene expression patterns;    Natural language processing;   

DOI  :  10.7717/peerj.15099

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

Keratins (KRTs) are the intermediate filament-forming proteins of epithelial cells, classified, according to their physicochemical properties, into “soft” and “hard” keratins. They have a key role in several aspects of cancer pathophysiology, including cancer cell invasion and metastasis, and several members of the KRT family serve as diagnostic or prognostic markers. The human genome contains both, functional KRT genes and non-functional KRT pseudogenes, arranged in two uninterrupted clusters on chromosomes 12 and 17. This characteristic renders KRTs ideal for evolutionary studies. Herein, comprehensive phylogenetic analyses of KRT homologous proteins in the genomes of major taxonomic divisions were performed, so as to fill a gap in knowledge regarding the functional implications of keratins in cancer biology among tumor-bearing species. The differential expression profiles of KRTs in diverse types of cancers were investigated by analyzing high-throughput data, as well. Several KRT genes, including the phylogenetically conserved ones, were found to be deregulated across several cancer types and to participate in a common protein-protein interaction network. This indicates that, at least in cancer-bearing species, these genes might have been under similar evolutionary pressure, perhaps to support the same important function(s). In addition, semantic relations between KRTs and cancer were detected through extensive text mining. Therefore, by applying an integrative in silico pipeline, the evolutionary history of KRTs was reconstructed in the context of cancer, and the potential of using non-mammalian species as model organisms in functional studies on human cancer-associated KRT genes was uncovered.

【 授权许可】

CC BY