2. Academic Validation
  3. Atypical cadherin CELSR2 acts as a therapeutic target for glioma through WNT3A/β-catenin signaling

Atypical cadherin CELSR2 acts as a therapeutic target for glioma through WNT3A/β-catenin signaling

  • Cell Death Dis. 2025 Nov 3;16(1):786. doi: 10.1038/s41419-025-08116-8.
Aimei Liu # 1 2,  Xin Geng # 3,  Xinyue Li 1,  Yue Xi 1,  Qing Han 1,  Xiangyu Wang 3,  Yajing Shen 4,  Libing Zhou 5 6 7 8 9
Affiliations

Affiliations

  • 1 School of Life Sciences and Health, University of Health and Rehabilitation Sciences, Qingdao, Shandong, P. R. China.
  • 2 Department of Pain, University of Health and Rehabilitation Sciences Qingdao Hospital (Qingdao Municipal Hospital), Qingdao, Shandong, P. R. China.
  • 3 Department of Neurosurgery, The First Affiliated Hospital of Jinan University, Guangzhou, P. R. China.
  • 4 School of Life Sciences and Health, University of Health and Rehabilitation Sciences, Qingdao, Shandong, P. R. China. [email protected].
  • 5 School of Life Sciences and Health, University of Health and Rehabilitation Sciences, Qingdao, Shandong, P. R. China. [email protected].
  • 6 Department of Neurosurgery, The First Affiliated Hospital of Jinan University, Guangzhou, P. R. China. [email protected].
  • 7 Guangdong-Hongkong-Macau CNS Regeneration Institute of Jinan University, Key Laboratory of CNS Regeneration (Ministry of Education), Guangdong Key Laboratory of Non-human Primate Research, Guangzhou, P. R. China. [email protected].
  • 8 Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu, P. R. China. [email protected].
  • 9 Center for Exercise and Brain Science, School of Psychology, Shanghai University of Sport, Shanghai, P.R. China. [email protected].
  • # Contributed equally.
PMID: 41184253 DOI: 10.1038/s41419-025-08116-8
Abstract

Glioma is the most common primary brain tumors and has a high recurrence and mortality rate after surgery. Most gliomas are of astrocytic origin. We recently demonstrated that Celsr2 is essential for injury-induced responses and functions of astrocytes, while its role in the development and treatment of gliomas remains unexplored. In this study, an increase of CELSR2 expression was identified in patient glioma samples and glioma cell lines, and higher levels of CELSR2 correlate with poorer patient survival as indicated by TCGA data. In cultured glioma cells, CELSR2 knockdown reduced proliferation and caused cell cycle arrest, which was further supported by proteomic analysis. CELSR2 knockdown inhibited Wnt/β-catenin signaling, and the effect could be reversed by activating β-catenin using GSK-3β Inhibitor in glioma cells. WNT3A efficiently enhanced the proliferation of glioma cells and activated the downstream signaling, which were significantly compromised by CELSR2 knockdown. We developed magnetic nanoparticles loaded with CELSR2-siRNA, which suppressed tumor growth in glioma-inoculated nude mice. In conclusion, CELSR2 positively regulates glioma development through WNT3A/β-catenin signaling and inhibiting CESLR2 is a novel therapeutic strategy for gliomas.

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