UGCG promotes chemoresistance and breast cancer progression via NF-κB and Wnt/β-catenin pathway activation
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 mechan...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-02-01
|
| Series: | Translational Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S193652332400367X |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832591830375464960 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Li Long |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-3ceb34a4f8e049d48ebfc866622d9808 |
| institution | Kabale University |
| issn | 1936-5233 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj-art-3ceb34a4f8e049d48ebfc866622d98082025-01-22T05:41:26ZengElsevierTranslational Oncology1936-52332025-02-0152102241UGCG promotes chemoresistance and breast cancer progression via NF-κB and Wnt/β-catenin pathway activationLi Long0Lei Wang1Yiran Liang2Fangzhou Ye3Yuhan Jin4Dan Luo5Xiaoyan Li6Yajie Wang7Yaming Li8Dianwen Han9Bing Chen10Wenjing Zhao11Lijuan Wang12Qifeng Yang13Department of Breast Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, PR China; Department of Breast Surgery, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang 621000, PR ChinaDepartment of Breast Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, PR ChinaDepartment of Breast Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, PR ChinaDepartment of Breast Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, PR ChinaDepartment of Breast Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, PR ChinaDepartment of Breast Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, PR ChinaDepartment of Breast Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, PR ChinaDepartment of Breast Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, PR ChinaDepartment of Breast Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, PR ChinaDepartment of Breast Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, PR ChinaBiological Resource Center, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, PR ChinaBiological Resource Center, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, PR ChinaBiological Resource Center, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, PR ChinaDepartment of Breast Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, PR China; Biological Resource Center, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, PR China; Research Institute of Breast Cancer, Shandong University, Jinan, Shandong, 250012, PR China; Corresponding author at: Department of Breast Surgery, General Surgery, Qilu Hospital of Shandong University, Wenhua Xi Road No. 107, Jinan 250012, Shandong, PR China.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.http://www.sciencedirect.com/science/article/pii/S193652332400367XBreast cancerChemoresistanceUGCGNF-κBWnt/β-catenin |
| spellingShingle | 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 UGCG promotes chemoresistance and breast cancer progression via NF-κB and Wnt/β-catenin pathway activation Translational Oncology Breast cancer Chemoresistance UGCG NF-κB Wnt/β-catenin |
| title | UGCG promotes chemoresistance and breast cancer progression via NF-κB and Wnt/β-catenin pathway activation |
| title_full | UGCG promotes chemoresistance and breast cancer progression via NF-κB and Wnt/β-catenin pathway activation |
| title_fullStr | UGCG promotes chemoresistance and breast cancer progression via NF-κB and Wnt/β-catenin pathway activation |
| title_full_unstemmed | UGCG promotes chemoresistance and breast cancer progression via NF-κB and Wnt/β-catenin pathway activation |
| title_short | UGCG promotes chemoresistance and breast cancer progression via NF-κB and Wnt/β-catenin pathway activation |
| title_sort | ugcg promotes chemoresistance and breast cancer progression via nf κb and wnt β catenin pathway activation |
| topic | Breast cancer Chemoresistance UGCG NF-κB Wnt/β-catenin |
| url | http://www.sciencedirect.com/science/article/pii/S193652332400367X |
| work_keys_str_mv | AT lilong ugcgpromoteschemoresistanceandbreastcancerprogressionvianfkbandwntbcateninpathwayactivation AT leiwang ugcgpromoteschemoresistanceandbreastcancerprogressionvianfkbandwntbcateninpathwayactivation AT yiranliang ugcgpromoteschemoresistanceandbreastcancerprogressionvianfkbandwntbcateninpathwayactivation AT fangzhouye ugcgpromoteschemoresistanceandbreastcancerprogressionvianfkbandwntbcateninpathwayactivation AT yuhanjin ugcgpromoteschemoresistanceandbreastcancerprogressionvianfkbandwntbcateninpathwayactivation AT danluo ugcgpromoteschemoresistanceandbreastcancerprogressionvianfkbandwntbcateninpathwayactivation AT xiaoyanli ugcgpromoteschemoresistanceandbreastcancerprogressionvianfkbandwntbcateninpathwayactivation AT yajiewang ugcgpromoteschemoresistanceandbreastcancerprogressionvianfkbandwntbcateninpathwayactivation AT yamingli ugcgpromoteschemoresistanceandbreastcancerprogressionvianfkbandwntbcateninpathwayactivation AT dianwenhan ugcgpromoteschemoresistanceandbreastcancerprogressionvianfkbandwntbcateninpathwayactivation AT bingchen ugcgpromoteschemoresistanceandbreastcancerprogressionvianfkbandwntbcateninpathwayactivation AT wenjingzhao ugcgpromoteschemoresistanceandbreastcancerprogressionvianfkbandwntbcateninpathwayactivation AT lijuanwang ugcgpromoteschemoresistanceandbreastcancerprogressionvianfkbandwntbcateninpathwayactivation AT qifengyang ugcgpromoteschemoresistanceandbreastcancerprogressionvianfkbandwntbcateninpathwayactivation |