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

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 severa...

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Main Authors: Işıl Takan, Gökhan Karakülah, Aikaterini Louka, Athanasia Pavlopoulou
Format: Article
Language:English
Published: PeerJ Inc. 2023-03-01
Series:PeerJ
Subjects:
Online Access:https://peerj.com/articles/15099.pdf
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author Işıl Takan
Gökhan Karakülah
Aikaterini Louka
Athanasia Pavlopoulou
author_facet Işıl Takan
Gökhan Karakülah
Aikaterini Louka
Athanasia Pavlopoulou
author_sort Işıl Takan
collection DOAJ
description 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.
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spelling doaj.art-a71d30a9a1564460948687a7f5d7d5722023-12-03T11:13:53ZengPeerJ Inc.PeerJ2167-83592023-03-0111e1509910.7717/peerj.15099“In the light of evolution:” keratins as exceptional tumor biomarkersIşıl Takan0Gökhan Karakülah1Aikaterini Louka2Athanasia Pavlopoulou3Izmir Biomedicine and Genome Center, Izmir, TurkeyIzmir Biomedicine and Genome Center, Izmir, TurkeyDNA Damage Laboratory, Department of Physics, School of Applied Mathematical and Physical Sciences, National Technical University of Athens, Athens, GreeceIzmir Biomedicine and Genome Center, Izmir, TurkeyKeratins (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.https://peerj.com/articles/15099.pdfCancerEvolutionComparative genomicsPhylogenyData miningInteraction network
spellingShingle Işıl Takan
Gökhan Karakülah
Aikaterini Louka
Athanasia Pavlopoulou
“In the light of evolution:” keratins as exceptional tumor biomarkers
PeerJ
Cancer
Evolution
Comparative genomics
Phylogeny
Data mining
Interaction network
title “In the light of evolution:” keratins as exceptional tumor biomarkers
title_full “In the light of evolution:” keratins as exceptional tumor biomarkers
title_fullStr “In the light of evolution:” keratins as exceptional tumor biomarkers
title_full_unstemmed “In the light of evolution:” keratins as exceptional tumor biomarkers
title_short “In the light of evolution:” keratins as exceptional tumor biomarkers
title_sort in the light of evolution keratins as exceptional tumor biomarkers
topic Cancer
Evolution
Comparative genomics
Phylogeny
Data mining
Interaction network
url https://peerj.com/articles/15099.pdf
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AT gokhankarakulah inthelightofevolutionkeratinsasexceptionaltumorbiomarkers
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AT athanasiapavlopoulou inthelightofevolutionkeratinsasexceptionaltumorbiomarkers