UGCG promotes chemoresistance and breast cancer progression via NF-κB and Wnt/β-catenin pathway activation

Bibliographic Details
Title: UGCG promotes chemoresistance and breast cancer progression via NF-κB and Wnt/β-catenin pathway activation
Authors: Li Long, Lei Wang, Yiran Liang, Fangzhou Ye, Yuhan Jin, Dan Luo, Xiaoyan Li, Yajie Wang, Yaming Li, Dianwen Han, Bing Chen, Wenjing Zhao, Lijuan Wang, Qifeng Yang
Source: Translational Oncology, Vol 52, Iss , Pp 102241- (2025)
Publisher Information: Elsevier, 2025.
Publication Year: 2025
Collection: LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Subject Terms: Breast cancer, Chemoresistance, UGCG, NF-κB, Wnt/β-catenin, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
More Details: Background: Taxane-based chemotherapy is the primary treatment for triple-negative breast cancer (TNBC), yet clinical outcomes remain unsatisfactory due to the persistence of chemoresistance. Identifying key factors that contribute to chemoresistance and understanding the associated molecular mechanisms is therefore essential. Method: The GEO databases were utilized to pinpoint factors related to chemoresistance, which were subsequently validated using clinical tissue samples. The role of UGCG in the malignant progression and chemoresistance of TNBC was assessed through various functional assays. Western blotting, qRT-PCR, and immunohistochemistry were employed to investigate the signaling pathways associated with UGCG in TNBC. Results: UGCG expression was notably elevated in chemoresistant breast cancer tissues and cells, as identified in GEO databases and confirmed through immunohistochemistry. Additionally, findings from our cohorts indicated that higher levels of UGCG expression correlated with a lower rate of pathological complete response (pCR), suggesting it could serve as an independent predictor of chemotherapy effectiveness. Gain- and loss-of-function experiments demonstrated that UGCG enhanced the proliferation, metastasis, and stemness of breast cancer cells. Furthermore, treatment with paclitaxel or docetaxel resulted in increased UGCG expression, which in turn reduced chemotherapy-induced cell apoptosis and improved drug resistance and metastatic capabilities. Mechanistically, UGCG was found to amplify the activation of NF-κB and Wnt/β-catenin pathways, and the use of inhibitors targeting these pathways diminished the UGCG-induced malignant effects. Conclusion: Our findings underscore the significant role of UGCG in the chemoresistance and progression of breast cancer, suggesting it as a predictive biomarker and potential therapeutic target to combat chemoresistance in this disease.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1936-5233
Relation: http://www.sciencedirect.com/science/article/pii/S193652332400367X; https://doaj.org/toc/1936-5233
DOI: 10.1016/j.tranon.2024.102241
Access URL: https://doaj.org/article/3ceb34a4f8e049d48ebfc866622d9808
Accession Number: edsdoj.3ceb34a4f8e049d48ebfc866622d9808
Database: Directory of Open Access Journals
More Details
ISSN:19365233
DOI:10.1016/j.tranon.2024.102241
Published in:Translational Oncology
Language:English