Open Access
ARTICLE
CBX4 Drives Gastric Cancer Progression by Activating β-Catenin Signaling
Wendong Jia#, Ting Zhang#, Ziying Zhang, Lingzhi Wu, Xihao Fu, Zhenxin Wang*, Ni Yin*
Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China
* Corresponding Author: Zhenxin Wang. Email: 
; Ni Yin. Email: 
# These authors contributed equally to this work
(This article belongs to the Special Issue: Signaling Pathway Crosstalk in Malignant Tumors: Molecular Targets and Combinatorial Therapeutics)
Oncology Research https://doi.org/10.32604/or.2025.068651
Received 03 June 2025; Accepted 27 August 2025; Published online 24 September 2025
Abstract
Objectives: 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. Methods: 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. Results: 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. Conclusion: 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.
Keywords
Gastric cancer (GC); chromobox 4 (CBX4); proliferation; metastasis; β-catenin
Login
Register
Submit a Paper
Propose a Special lssue
Download PDF
Downloads
Citation Tools
