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

## TL;DR

This study identifies CELSR2 as a potential therapeutic target for gliomas by showing its role in promoting tumor growth through WNT3A/β-catenin signaling.

## Contribution

The novel contribution is identifying CELSR2 as a glioma therapeutic target via its regulation of WNT3A/β-catenin signaling.

## Key findings

- CELSR2 expression is elevated in glioma samples and correlates with poor patient survival.
- CELSR2 knockdown inhibits glioma cell proliferation and Wnt/β-catenin signaling.
- Magnetic nanoparticles loaded with CELSR2-siRNA suppressed tumor growth in mice.

## 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.