Presenilin1 inhibits glioblastoma cell invasiveness via promoting Sortilin cleavage

Abstract Background Alzheimer’s disease (AD) and glioblastoma are the most common and devastating diseases in the neurology and neurosurgery departments, respectively. Our previous research reports that the AD-related protein Presenilin1 represses cell proliferation by inhibiting the Wnt/β-catenin p...

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Autores principales:	Wei Yang, Yan Xiang, Mao-Jun Liao, Peng-Fei Wu, Lin Yang, Guo-Hao Huang, Bao-Zhong Shi, Liang Yi, Sheng-Qing Lv
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Presenilin1 Cleavage Sortilin Glioblastoma Invasion Medicine R Cytology QH573-671
Acceso en línea:	https://doaj.org/article/a11393aa34b849108ff50c609a5f3e80
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spelling	oai:doaj.org-article:a11393aa34b849108ff50c609a5f3e802021-11-21T12:13:39ZPresenilin1 inhibits glioblastoma cell invasiveness via promoting Sortilin cleavage10.1186/s12964-021-00780-51478-811Xhttps://doaj.org/article/a11393aa34b849108ff50c609a5f3e802021-11-01T00:00:00Zhttps://doi.org/10.1186/s12964-021-00780-5https://doaj.org/toc/1478-811XAbstract Background Alzheimer’s disease (AD) and glioblastoma are the most common and devastating diseases in the neurology and neurosurgery departments, respectively. Our previous research reports that the AD-related protein Presenilin1 represses cell proliferation by inhibiting the Wnt/β-catenin pathway in glioblastoma. However, the function of Presenilin1 and the underlying mechanism need to be further investigated. Methods The correlations of two genes were conducted on the R2 microarray platform and CGGA. Wound healing, Transwell assays and glioblastoma transplantation were performed to detect invasion ability. Phalloidin staining was employed to show cell morphology. Proximity ligation assays and protein docking assays were employed to detect two protein locations. We also employed western blotting to detect protein expression. Results We found that Presenilin1 clearly repressed the migration, invasion and mesenchymal transition of glioblastoma cells. Intriguingly, we observed that the expression of Presenilin1 was positively correlated with Sortilin, which is identified as a pro-invasion molecule in glioma. Furthermore, Presenilin1 interacted with Sortilin at the transmembrane domain and repressed Sortilin expression by cleaving it in glioblastoma cells. First, we found that Sortilin introduced the function of Presenilin1 in phosphorylating β-catenin and repressing invasion in glioblastoma cells. Last, Presenilin1 stimulation sharply suppressed the invasion and mesenchymal transition of glioblastoma in mouse subcutaneous and intracranial transplantation models. Conclusions Our study reveals that Sortilin mediates the regulation of β-catenin by Presenilin1 and transduces the anti-invasive function of Presenilin1, which may provide novel therapeutic targets for glioblastoma treatment. Video AbstractWei YangYan XiangMao-Jun LiaoPeng-Fei WuLin YangGuo-Hao HuangBao-Zhong ShiLiang YiSheng-Qing LvBMCarticlePresenilin1CleavageSortilinGlioblastomaInvasionMedicineRCytologyQH573-671ENCell Communication and Signaling, Vol 19, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Presenilin1 Cleavage Sortilin Glioblastoma Invasion Medicine R Cytology QH573-671
spellingShingle	Presenilin1 Cleavage Sortilin Glioblastoma Invasion Medicine R Cytology QH573-671 Wei Yang Yan Xiang Mao-Jun Liao Peng-Fei Wu Lin Yang Guo-Hao Huang Bao-Zhong Shi Liang Yi Sheng-Qing Lv Presenilin1 inhibits glioblastoma cell invasiveness via promoting Sortilin cleavage
description	Abstract Background Alzheimer’s disease (AD) and glioblastoma are the most common and devastating diseases in the neurology and neurosurgery departments, respectively. Our previous research reports that the AD-related protein Presenilin1 represses cell proliferation by inhibiting the Wnt/β-catenin pathway in glioblastoma. However, the function of Presenilin1 and the underlying mechanism need to be further investigated. Methods The correlations of two genes were conducted on the R2 microarray platform and CGGA. Wound healing, Transwell assays and glioblastoma transplantation were performed to detect invasion ability. Phalloidin staining was employed to show cell morphology. Proximity ligation assays and protein docking assays were employed to detect two protein locations. We also employed western blotting to detect protein expression. Results We found that Presenilin1 clearly repressed the migration, invasion and mesenchymal transition of glioblastoma cells. Intriguingly, we observed that the expression of Presenilin1 was positively correlated with Sortilin, which is identified as a pro-invasion molecule in glioma. Furthermore, Presenilin1 interacted with Sortilin at the transmembrane domain and repressed Sortilin expression by cleaving it in glioblastoma cells. First, we found that Sortilin introduced the function of Presenilin1 in phosphorylating β-catenin and repressing invasion in glioblastoma cells. Last, Presenilin1 stimulation sharply suppressed the invasion and mesenchymal transition of glioblastoma in mouse subcutaneous and intracranial transplantation models. Conclusions Our study reveals that Sortilin mediates the regulation of β-catenin by Presenilin1 and transduces the anti-invasive function of Presenilin1, which may provide novel therapeutic targets for glioblastoma treatment. Video Abstract
format	article
author	Wei Yang Yan Xiang Mao-Jun Liao Peng-Fei Wu Lin Yang Guo-Hao Huang Bao-Zhong Shi Liang Yi Sheng-Qing Lv
author_facet	Wei Yang Yan Xiang Mao-Jun Liao Peng-Fei Wu Lin Yang Guo-Hao Huang Bao-Zhong Shi Liang Yi Sheng-Qing Lv
author_sort	Wei Yang
title	Presenilin1 inhibits glioblastoma cell invasiveness via promoting Sortilin cleavage
title_short	Presenilin1 inhibits glioblastoma cell invasiveness via promoting Sortilin cleavage
title_full	Presenilin1 inhibits glioblastoma cell invasiveness via promoting Sortilin cleavage
title_fullStr	Presenilin1 inhibits glioblastoma cell invasiveness via promoting Sortilin cleavage
title_full_unstemmed	Presenilin1 inhibits glioblastoma cell invasiveness via promoting Sortilin cleavage
title_sort	presenilin1 inhibits glioblastoma cell invasiveness via promoting sortilin cleavage
publisher	BMC
publishDate	2021
url	https://doaj.org/article/a11393aa34b849108ff50c609a5f3e80
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Presenilin1 inhibits glioblastoma cell invasiveness via promoting Sortilin cleavage

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