1. Academic Validation
  2. Presenilin1 inhibits glioblastoma cell invasiveness via promoting Sortilin cleavage

Presenilin1 inhibits glioblastoma cell invasiveness via promoting Sortilin cleavage

  • Cell Commun Signal. 2021 Nov 15;19(1):112. doi: 10.1186/s12964-021-00780-5.
Wei Yang  # 1 Yan Xiang  # 1 Mao-Jun Liao 2 Peng-Fei Wu 2 Lin Yang 1 Guo-Hao Huang 1 Bao-Zhong Shi 3 Liang Yi 4 Sheng-Qing Lv 5
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Xinqiao Hospital, Army Medical University, 183# Xinqiao street, Shapingba District, Chongqing, 400037, China.
  • 2 Department of Neurosurgery, Daping Hospital, Army Medical University, 10# Changjiangzhi Road, Daping, Yuzhong District, Chongqing, 400042, China.
  • 3 Department of Critical Care Medicine & Department of Neurosurgery, The First Affiliated Hospital & College of Clinical Medical, Henan University of Science and Technology, Luoyang, 471003, Henan, China.
  • 4 Department of Neurosurgery, Daping Hospital, Army Medical University, 10# Changjiangzhi Road, Daping, Yuzhong District, Chongqing, 400042, China. happyape@126.com.
  • 5 Department of Neurosurgery, Xinqiao Hospital, Army Medical University, 183# Xinqiao street, Shapingba District, Chongqing, 400037, China. lvsq0518@hotmail.com.
  • # Contributed equally.
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.

Keywords

Cleavage; Glioblastoma; Invasion; Presenilin1; Sortilin.

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