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Evolution of higher mesenchymal CD44 expression in the human lineage: A gene linked to cancer malignancy

CD44 is an extracellular matrix receptor implicated in cancer progression. CD44 increases the invasibility of skin (SF) and endometrial stromal fibroblasts (ESF) by cancer and trophoblast cells. We reasoned that the evolution of CD44 expression can affect both, the fetal–maternal interaction through...

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Autores principales: Ma, Xinghong, Dighe, Anasuya, Maziarz, Jamie, Neumann, Edwin, Erkenbrack, Eric, Hei, Yuan-Yuan, Liu, Yansheng, Suhail, Yasir, Pak, Irene, Levchenko, Andre, Wagner, Günter P
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9487634/
https://www.ncbi.nlm.nih.gov/pubmed/36148042
http://dx.doi.org/10.1093/emph/eoac036
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author Ma, Xinghong
Dighe, Anasuya
Maziarz, Jamie
Neumann, Edwin
Erkenbrack, Eric
Hei, Yuan-Yuan
Liu, Yansheng
Suhail, Yasir
Pak, Irene
Levchenko, Andre
Wagner, Günter P
author_facet Ma, Xinghong
Dighe, Anasuya
Maziarz, Jamie
Neumann, Edwin
Erkenbrack, Eric
Hei, Yuan-Yuan
Liu, Yansheng
Suhail, Yasir
Pak, Irene
Levchenko, Andre
Wagner, Günter P
author_sort Ma, Xinghong
collection PubMed
description CD44 is an extracellular matrix receptor implicated in cancer progression. CD44 increases the invasibility of skin (SF) and endometrial stromal fibroblasts (ESF) by cancer and trophoblast cells. We reasoned that the evolution of CD44 expression can affect both, the fetal–maternal interaction through CD44 in ESF as well as vulnerability to malignant cancer through expression in SF. We studied the evolution of CD44 expression in mammalian SF and ESF and demonstrate that in the human lineage evolved higher CD44 expression. Isoform expression in cattle and human is very similar suggesting that differences in invasibility are not due to the nature of expressed isoforms. We then asked whether the concerted gene expression increase in both cell types is due to shared regulatory mechanisms or due to cell type-specific factors. Reporter gene experiments with cells and cis-regulatory elements from human and cattle show that the difference of CD44 expression is due to cis effects as well as cell type-specific trans effects. These results suggest that the concerted expression increase is likely due to selection acting on both cell types because the evolutionary change in cell type-specific factors requires selection on cell type-specific functions. This scenario implies that the malignancy enhancing effects of elevated CD44 expression in humans likely evolved as a side-effect of positive selection on a yet unidentified other function of CD44. A possible candidate is the anti-fibrotic effect of CD44 but there are no reliable data showing that humans and primates are less fibrotic than other mammals.
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spelling pubmed-94876342022-09-21 Evolution of higher mesenchymal CD44 expression in the human lineage: A gene linked to cancer malignancy Ma, Xinghong Dighe, Anasuya Maziarz, Jamie Neumann, Edwin Erkenbrack, Eric Hei, Yuan-Yuan Liu, Yansheng Suhail, Yasir Pak, Irene Levchenko, Andre Wagner, Günter P Evol Med Public Health Original Research Article CD44 is an extracellular matrix receptor implicated in cancer progression. CD44 increases the invasibility of skin (SF) and endometrial stromal fibroblasts (ESF) by cancer and trophoblast cells. We reasoned that the evolution of CD44 expression can affect both, the fetal–maternal interaction through CD44 in ESF as well as vulnerability to malignant cancer through expression in SF. We studied the evolution of CD44 expression in mammalian SF and ESF and demonstrate that in the human lineage evolved higher CD44 expression. Isoform expression in cattle and human is very similar suggesting that differences in invasibility are not due to the nature of expressed isoforms. We then asked whether the concerted gene expression increase in both cell types is due to shared regulatory mechanisms or due to cell type-specific factors. Reporter gene experiments with cells and cis-regulatory elements from human and cattle show that the difference of CD44 expression is due to cis effects as well as cell type-specific trans effects. These results suggest that the concerted expression increase is likely due to selection acting on both cell types because the evolutionary change in cell type-specific factors requires selection on cell type-specific functions. This scenario implies that the malignancy enhancing effects of elevated CD44 expression in humans likely evolved as a side-effect of positive selection on a yet unidentified other function of CD44. A possible candidate is the anti-fibrotic effect of CD44 but there are no reliable data showing that humans and primates are less fibrotic than other mammals. Oxford University Press 2022-08-30 /pmc/articles/PMC9487634/ /pubmed/36148042 http://dx.doi.org/10.1093/emph/eoac036 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of the Foundation for Evolution, Medicine, and Public Health. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Research Article
Ma, Xinghong
Dighe, Anasuya
Maziarz, Jamie
Neumann, Edwin
Erkenbrack, Eric
Hei, Yuan-Yuan
Liu, Yansheng
Suhail, Yasir
Pak, Irene
Levchenko, Andre
Wagner, Günter P
Evolution of higher mesenchymal CD44 expression in the human lineage: A gene linked to cancer malignancy
title Evolution of higher mesenchymal CD44 expression in the human lineage: A gene linked to cancer malignancy
title_full Evolution of higher mesenchymal CD44 expression in the human lineage: A gene linked to cancer malignancy
title_fullStr Evolution of higher mesenchymal CD44 expression in the human lineage: A gene linked to cancer malignancy
title_full_unstemmed Evolution of higher mesenchymal CD44 expression in the human lineage: A gene linked to cancer malignancy
title_short Evolution of higher mesenchymal CD44 expression in the human lineage: A gene linked to cancer malignancy
title_sort evolution of higher mesenchymal cd44 expression in the human lineage: a gene linked to cancer malignancy
topic Original Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9487634/
https://www.ncbi.nlm.nih.gov/pubmed/36148042
http://dx.doi.org/10.1093/emph/eoac036
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