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Glioblastoma-secreted soluble CD44 activates tau pathology in the brain
During aggressive tumor growth and migration, glioblastoma cells secrete diverse molecules and adhesion proteins to the extracellular matrix. Yet, the biochemical effects of the glioblastoma secretome in the brain remain largely unknown. Here we show that soluble CD44 secreted from glioblastoma cell...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5938049/ https://www.ncbi.nlm.nih.gov/pubmed/29622771 http://dx.doi.org/10.1038/s12276-017-0008-7 |
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author | Lim, Sungsu Kim, Dohee Ju, Shinyeong Shin, Seulgi Cho, Il-joo Park, Sung-Hye Grailhe, Regis Lee, Cheolju Kim, Yun Kyung |
author_facet | Lim, Sungsu Kim, Dohee Ju, Shinyeong Shin, Seulgi Cho, Il-joo Park, Sung-Hye Grailhe, Regis Lee, Cheolju Kim, Yun Kyung |
author_sort | Lim, Sungsu |
collection | PubMed |
description | During aggressive tumor growth and migration, glioblastoma cells secrete diverse molecules and adhesion proteins to the extracellular matrix. Yet, the biochemical effects of the glioblastoma secretome in the brain remain largely unknown. Here we show that soluble CD44 secreted from glioblastoma cells induces neuronal degeneration through the activation of tau pathology in the brain. Glioblastoma-xenograft tissues showed a number of degenerating neurons bearing highly phosphorylated tau. Through a series of secretome-analyses, we identified that soluble CD44 was the responsible protein inducing tau phosphorylation and aggregation (EC(50) = 19.1 ng/mL). The treatment of sCD44 to primary hippocampal neurons-induced tau hyperphosphorylation, leading to neuronal degeneration. Also, the injection of sCD44 into the brains of tau transgenic mice induced tau hyper-phosphorylation in hippocampal neurons. Altogether, our data suggest a neurodegenerative role of sCD44 in promoting tau pathology and serving as a molecular link between glioblastoma and neurodegeneration. |
format | Online Article Text |
id | pubmed-5938049 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-59380492018-05-15 Glioblastoma-secreted soluble CD44 activates tau pathology in the brain Lim, Sungsu Kim, Dohee Ju, Shinyeong Shin, Seulgi Cho, Il-joo Park, Sung-Hye Grailhe, Regis Lee, Cheolju Kim, Yun Kyung Exp Mol Med Article During aggressive tumor growth and migration, glioblastoma cells secrete diverse molecules and adhesion proteins to the extracellular matrix. Yet, the biochemical effects of the glioblastoma secretome in the brain remain largely unknown. Here we show that soluble CD44 secreted from glioblastoma cells induces neuronal degeneration through the activation of tau pathology in the brain. Glioblastoma-xenograft tissues showed a number of degenerating neurons bearing highly phosphorylated tau. Through a series of secretome-analyses, we identified that soluble CD44 was the responsible protein inducing tau phosphorylation and aggregation (EC(50) = 19.1 ng/mL). The treatment of sCD44 to primary hippocampal neurons-induced tau hyperphosphorylation, leading to neuronal degeneration. Also, the injection of sCD44 into the brains of tau transgenic mice induced tau hyper-phosphorylation in hippocampal neurons. Altogether, our data suggest a neurodegenerative role of sCD44 in promoting tau pathology and serving as a molecular link between glioblastoma and neurodegeneration. Nature Publishing Group UK 2018-04-06 /pmc/articles/PMC5938049/ /pubmed/29622771 http://dx.doi.org/10.1038/s12276-017-0008-7 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, and provide a link to the Creative Commons license. You do not have permission under this license to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/. |
spellingShingle | Article Lim, Sungsu Kim, Dohee Ju, Shinyeong Shin, Seulgi Cho, Il-joo Park, Sung-Hye Grailhe, Regis Lee, Cheolju Kim, Yun Kyung Glioblastoma-secreted soluble CD44 activates tau pathology in the brain |
title | Glioblastoma-secreted soluble CD44 activates tau pathology in the brain |
title_full | Glioblastoma-secreted soluble CD44 activates tau pathology in the brain |
title_fullStr | Glioblastoma-secreted soluble CD44 activates tau pathology in the brain |
title_full_unstemmed | Glioblastoma-secreted soluble CD44 activates tau pathology in the brain |
title_short | Glioblastoma-secreted soluble CD44 activates tau pathology in the brain |
title_sort | glioblastoma-secreted soluble cd44 activates tau pathology in the brain |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5938049/ https://www.ncbi.nlm.nih.gov/pubmed/29622771 http://dx.doi.org/10.1038/s12276-017-0008-7 |
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