CD146通过抑制DCBLD2降解和激活AKT通路来促进乳腺瘤的恶性进展
Jiewen Chen1,2,3, Qingji Xu4,5, Dan Liu4
1Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China.
CD146通过稳定DCBLD2和激活PI3K/AKT通路来促进乳腺恶性乳腺瘤 (PT) 的进展. 用抗体AA98准CD146抑制了瘤生长,确定CD146作为预后标记物和治疗标.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 乳腺恶性乳腺瘤 (PTs) 具有侵略性,治疗选择有限.
- 迫切需要有效的预后标志物和PT治疗点.
研究的目的:
- 研究CD146在促进PT恶性进展中的作用和机制.
- 确定CD146作为潜在的预后标记物和乳腺恶性PT的治疗点.
主要方法:
- 单细胞RNA测序 (scRNA-seq),免疫染色和实时PCR被用于分析CD146的表达.
- 功能性测试 (增殖,侵入,原收缩) 和体内模型 (有机体,PDX) 评估了CD146的作用和治疗潜力.
- 转录基因,蛋白质基因,共免疫沉和拉下测试确定了潜在的分子机制.
主要成果:
- 恶性PT中CD146表达率升高,并与复发风险相关.
- 通过保护DCBLD2免受降解,激活PI3K/AKT通路,CD146增强了PT细胞的活力和侵入性.
- 反CD146抗体AA98在有机体和PDX模型中显著抑制恶性PT生长.
结论:
- 通过CD146-DCBLD2/PI3K/AKT轴,CD146是恶性PT进展的关键驱动因素.
- CD146作为一个有前途的预后标志物和治疗目标,用于乳腺恶性PTs.
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