Glioblastoma-secreted soluble CD44 activates tau pathology in the brain

Title
Glioblastoma-secreted soluble CD44 activates tau pathology in the brain
Authors
이철주조일주김윤경신슬기김도희임성수주신영박성혜Regis Grailhe
Keywords
퇴행성 뇌질환; 교모세포종; 타우인산화; 신경퇴행; CD44
Issue Date
2018-04
Publisher
Experimental & molecular medicine
Citation
VOL 50, NO 5-11
Abstract
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 (EC50 = 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.
URI
http://pubs.kist.re.kr/handle/201004/67244
ISSN
1226-3613
Appears in Collections:
KIST Publication > Article
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE