# GLIS2 Promotes Epithelial‐Mesenchymal Transition and Gastric Cancer Progression by Regulating BGN to Activate the Wnt/β‐Catenin Pathway

## TL;DR

This study shows how GLIS2 promotes gastric cancer by activating a pathway involving BGN and Wnt/β-catenin, offering new therapeutic targets.

## Contribution

The study identifies a novel GLIS2-BGN-Wnt/β-catenin axis in gastric cancer progression and epithelial-mesenchymal transition.

## Key findings

- GLIS2 enhances BGN transcription, activating Wnt/β-catenin signaling in gastric cancer cells.
- BGN overexpression reverses the effects of GLIS2 knockdown, confirming its role in tumor promotion.
- The Wnt/β-catenin inhibitor XAV-939 blocks BGN's tumor-promoting effects, suggesting therapeutic potential.

## Abstract

This study elucidates the mechanism by which GLIS Family Zinc Finger 2 (GLIS2) promotes epithelial‐mesenchymal transition (EMT) in gastric cancer through biglycan (BGN) activation and Wnt/β‐catenin stimulation. By analyzing 18 pairs of GC tissues and establishing in vitro models (combining GLIS2 knockdown/BGN overexpression with Wnt pathway modulators), we demonstrated that GLIS2 directly binds to the BGN promoter to enhance its transcription, thereby activating Wnt/β‐catenin signaling and significantly promoting GC cell migration, invasion, and EMT. Functional rescue experiments confirmed that BGN overexpression reverses the inhibitory effects of GLIS2 knockdown, while the Wnt/β‐catenin inhibitor XAV‐939 effectively blocks BGN's tumor‐promoting effects. These findings establish the crucial role of the GLIS2‐BGN‐Wnt/β‐catenin axis in regulating GC EMT and identify novel potential therapeutic targets for GC treatment.