# Identification and validation of the potential therapeutic value of CASK in osteosarcoma: a computational analysis and in vitro experiments

**Authors:** Hongjuan Yang, Weiying Zhong, Danping Shen, Sihui Chen

PMC · DOI: 10.3389/fonc.2026.1693570 · 2026-03-16

## TL;DR

This study explores CASK's role in osteosarcoma, showing it may be a new target for treatment by affecting cancer cell growth and immune responses.

## Contribution

The study identifies CASK as a novel potential therapeutic target in osteosarcoma through computational and experimental validation.

## Key findings

- CASK is significantly upregulated in osteosarcoma samples.
- Inhibiting CASK promotes apoptosis and inhibits cell cycle progression in osteosarcoma cells.
- CASK is linked to immune processes and the JAK/STAT signaling pathway, particularly with Macrophages_M2.

## Abstract

Currently, identifying new therapeutic targets in clinical practice is crucial for improving the treatment of osteosarcoma. The abnormal expression of calcium/calmodulin-dependent serine protein kinase (CASK) plays an important role in the tumorigenesis of many cancers; however, the role of CASK in the potential therapeutic value of osteosarcoma has not been reported.

The Gene Expression Omnibus (GEO) database was used to analyze the expression levels of CASK in osteosarcoma patients. Cell experiments validated the role of CASK in osteosarcoma cells and revealed the potential mechanism of action of CASK from three aspects: immunity, pathogenic gene expression, and protein interaction.

The results showed that CASK was significantly upregulated in osteosarcoma samples. Inhibiting the expression of CASK can significantly promote cell apoptosis and inhibit the cycle progression of osteosarcoma cells. The high expression of CASK is mainly enriched in the immune system process, the JAK/STAT signaling pathway. There is a significant positive correlation between CASK and Macrophages_M2. Changes in CASK expression levels may activate the JAK/STAT signaling pathway by affecting the immunity of Macrophages_M2, thereby regulating apoptosis and cell cycle progression in osteosarcoma cells.

In conclusion, CASK may be a potential therapeutic target for osteosarcoma patients.

## Linked entities

- **Genes:** CASK (calcium/calmodulin dependent serine protein kinase) [NCBI Gene 8573]
- **Diseases:** osteosarcoma (MONDO:0002623)

## Full-text entities

- **Genes:** CASK (calcium/calmodulin dependent serine protein kinase) [NCBI Gene 8573] {aka CAGH39, CAMGUK, CMG, FGS4, LIN2, MICPCH}
- **Diseases:** osteosarcoma (MESH:D012516), cancers (MESH:D009369)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

10 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13033479/full.md

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Source: https://tomesphere.com/paper/PMC13033479