# CBX4 Drives Gastric Cancer Progression by Activating β-Catenin Signaling

## TL;DR

CBX4 promotes gastric cancer growth by activating β-catenin signaling, suggesting it could be a new target for cancer treatments.

## Contribution

This study identifies CBX4 as a driver of gastric cancer progression through β-catenin signaling activation.

## Key findings

- CBX4 is upregulated in gastric cancer tissues and correlates with aggressive tumor traits.
- CBX4 overexpression enhances cancer cell proliferation and invasion, while its depletion suppresses these traits.
- CBX4 activates β-catenin signaling, and inhibiting this pathway reduces CBX4-induced cancer progression.

## Abstract

Chromobox 4 (CBX4), a polycomb protein family member linked to tumor pathogenesis via dysregulation, has an incompletely defined role in gastric cancer (GC). The study aimed to investigate the role and mechanism of CBX4 in GC progression and evaluate its potential as a therapeutic target.

CBX4 expression was assessed in GC tissues vs. adjacent non-cancerous tissues and in GC cell lines vs. normal gastric mucosal epithelial cells. Clinicopathological correlations were analyzed. Functional impacts of CBX4 were determined using knockdown and overexpression models in vitro (cell proliferation, migration, invasion) and in vivo (xenograft tumorigenesis in nude mice). Mechanistic studies evaluated β-catenin levels (total and nuclear) and transcriptional activity following CBX4 modulation. The functional dependency on Wnt/β-catenin signaling was tested using the pharmacological inhibitor XAV939 in CBX4-overexpressing cells.

CBX4 expression was significantly upregulated in GC tissues and cell lines. Elevated CBX4 levels strongly correlated with aggressive tumor characteristics, including larger tumor size, lymph node metastasis, and advanced Tumor, Node, Metastasis (TNM) stage. Functionally, CBX4 knockdown suppressed GC cell proliferation, migration, invasion in vitro, and tumorigenesis in vivo. Conversely, CBX4 overexpression enhanced these malignant traits. Mechanistically, CBX4 depletion reduced total and nuclear β-catenin levels and inhibited its transcriptional activity, while CBX4 overexpression had the opposite effect. Critically, XAV939-mediated inhibition of Wnt/β-catenin signaling attenuated the oncogenic effects induced by CBX4 overexpression.

CBX4 upregulation promotes GC progression via β-catenin signaling activation. The CBX4/β-catenin axis emerges as a promising therapeutic target, offering potential for the development of precision treatment strategies in GC management.