# The CHI3L1 protein plays role as a protecting factor against autophagy in glioblastoma cells

## TL;DR

This study shows that the CHI3L1 protein protects glioblastoma cells from autophagy, suggesting that inhibiting it could be a new treatment strategy.

## Contribution

The novel finding is that CHI3L1 inhibition induces autophagy in glioblastoma cells, offering a potential new therapeutic approach.

## Key findings

- CHI3L1 inhibition leads to increased autophagy in glioblastoma cells.
- CHI3L1 expression changes in response to cell starvation and X-ray doses.
- Inhibiting CHI3L1 could be a new therapy to upregulate autophagy in glioblastoma.

## Abstract

The CHI3L1 protein supports various types of cancer progression and metastasis, where the background players were the upregulation of angiogenesis and microenvironment modulation. In glioblastoma (GB), high vascularisation is a key feature of these tumours, making anti-angiogenic therapy a pivotal treatment option. Autophagy, a dual-faced mechanism, may be useful as a target in GB treatment. This work presents the role of the CHI3L1 protein in autophagy in GB. U-87 MG glioblastoma cells and a GB spheroid model consisting of U-87 MG cells, macrophages and endothelial cells were used in the studies. A new tissue-like phantom was designed for the radiotherapy of spheroids. The role of CHI3L1 in autophagy regulation was analysed after cell starvation and treatment with G721-0282, a small molecule inhibitor of CHI3L1, as well as X-ray doses. The biological responses were evaluated using the Western blot method, immunohistochemical reactions, DHT (digital holographic tomography) and O-PTIR (optical phototermal infrared spectroscopy) to analyse biological responses in GB spheroids. Induction of autophagy in glioblastoma cells after CHI3L1 inhibition was observed, as well changes in CHI3L1 expression levels occurred after cell starvation and different X-ray radiation doses. Secondary structure changes in glycoproteins and decreases in nucleic acids were observed in O-PTIR. The expression of CHI3L1 in glioblastoma cells may be precisely regulated by an adverse environment, such as nutrient depletion or anti-tumour treatment. Inhibiting the CHI3L1 protein leads to upregulation of autophagy, meaning that CHI3L1 inhibitors could be used as a new therapy to upregulate autophagy in GB.

The online version contains supplementary material available at 10.1007/s10495-026-02319-w.