UGCG通过激活NF-κB和Wnt/β-catenin通路促进化疗抗性和乳腺癌进展。

IF 4.5 2区 医学 Q1 ONCOLOGY
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
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引用次数: 0

摘要

背景:以紫杉类药物为基础的化疗是三阴性乳腺癌(TNBC)的主要治疗方法,但由于化疗耐药性的持续存在,临床疗效仍不尽如人意。因此,找出导致化疗耐药的关键因素并了解相关的分子机制至关重要:方法:利用 GEO 数据库找出与化疗耐药性相关的因素,随后利用临床组织样本对这些因素进行了验证。通过各种功能测定评估了UGCG在TNBC恶性进展和化疗耐药性中的作用。研究人员采用了Western印迹、qRT-PCR和免疫组化等方法研究TNBC中与UGCG相关的信号通路:结果:经 GEO 数据库鉴定和免疫组化证实,UGCG 在化疗耐受性乳腺癌组织和细胞中的表达明显升高。此外,我们的研究结果表明,较高水平的UGCG表达与较低的病理完全反应率(pCR)相关,这表明它可以作为化疗效果的独立预测因子。功能增益和功能缺失实验表明,UGCG能增强乳腺癌细胞的增殖、转移和干性。此外,紫杉醇或多西他赛治疗会导致 UGCG 表达增加,进而减少化疗诱导的细胞凋亡,提高耐药性和转移能力。从机理上讲,UGCG可扩大NF-κB和Wnt/β-catenin通路的活化,而使用针对这些通路的抑制剂可减轻UGCG诱导的恶性效应:我们的研究结果强调了UGCG在乳腺癌化疗耐药性和病情进展中的重要作用,并将其作为一种预测性生物标志物和潜在的治疗靶点,以对抗该疾病的化疗耐药性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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 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.

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来源期刊
Translational Oncology
Translational Oncology Biochemistry, Genetics and Molecular Biology-Cancer Research
CiteScore
7.20
自引率
2.00%
发文量
314
审稿时长
6-12 weeks
期刊介绍: Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.
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