Work

CBX2 promotes cisplatin resistance in ovarian cancer via SIAH2-mediated β-catenin stabilization and ATG9B-dependent autophagy activation

Year: 2026

Type: article

Abstract: Platinum-based chemotherapy is the first-line therapeutic strategy for ovarian cancer (OC), and resistance to it adversely affects most OC patients. CBX2 plays an essential role in cancer progression and is widely thought to be involved in cisplatin (DDP) resistance. This study aimed to investigate the molecular mechanism of CBX2 in DDP resistance in OC. The human normal ovarian epithelial cell line (IOSE80) and OC cell lines (SK-OV-3 and OVcar3) were used. The functions of CBX2 and ATG9B were explored by transfecting overexpression and silencing plasmids into OC cells. Drug-resistant DDP OC cell lines were established. Real-time quantitative PCR (qPCR), Western blotting, and immunofluorescence (IF) analysis were conducted to evaluate the molecular expression at the mRNA and protein levels. The Cell Counting Kit-8 (CCK-8) assay measured the IC 50 value of cells under DDP treatment. Flow cytometry was used to determine cell apoptosis, and a colony formation assay was used to measure cell proliferation. A co-immunoprecipitation (Co-IP) assay evaluated the binding relationship between SIAH2 and β-catenin. CBX2 was highly expressed in OC and was associated with DDP resistance. Besides, CBX2 overexpression enhanced DDP resistance and autophagy in OC cells. As expected, CBX2 silencing suppressed autophagy and DDP resistance in OC cells. Mechanistically, CBX2 stabilized β-catenin by inhibiting ubiquitin-mediated degradation. Inhibiting the Wnt/β-catenin pathway suppressed CBX2-induced autophagy and decreased DDP resistance in OC cells. Activating the Wnt/β-catenin pathway promoted CBX2-induced autophagy and increased DDP resistance in OC cells. ATG9B mediated CBX2-induced autophagy and DDP resistance. Finally, ATG9B inhibition rescued the effects of CBX2-mediated autophagy and DDP resistance. CBX2 promotes cisplatin resistance in OC via SIAH2-mediated β-catenin stabilization and ATG9B-dependent autophagy activation. Overall, our study reveals a hitherto undocumented role of CBX2 in mediating DDP resistance, providing insights for potential therapeutic biomarkers to overcome DDP resistance in OC.

Source: Journal of Ovarian Research

DOI: 10.1186/s13048-025-01944-4

Authors: Xinxin Kou, Lijie Dong, Zheng Zhao, Xiaoxia Yang, Yuanjing Hu

Institutions: Zhengzhou University, Henan Cancer Hospital, Tianjin Medical University, Tianjin Central Hospital of Gynecology Obstetrics

Language: English

Topic: Wnt/β-catenin signaling in development and cancer

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,290