通过控制HIF1α通路,XBP1促进了三阴性乳腺癌的发生
Xi Chen1, Dimitrios Iliopoulos2,3, Qing Zhang4
1Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065.
Nature
|March 28, 2014
概括
展开蛋白质响应 (UPR) 传感器XBP1在三阴性乳腺癌 (TNBC) 中被激活. 向XBP1可能通过抑制瘤生长和进展,为这种侵略性癌症提供新的治疗方法.
科学领域:
- 分子生物学分子生物学
- 在瘤学瘤学.
- 细胞应激反应的应激反应
背景情况:
- 癌细胞激活适应性途径,包括未展开的蛋白质反应 (UPR),以在不良血管化的压力下生存.
- 由IRE1和XBP1介导的UPR在各种瘤中发现,但XBP1在乳腺上皮细胞中的作用尚不清楚.
- 三阴性乳腺癌 (TNBC) 具有侵略性,治疗选择有限.
研究的目的:
- 研究XBP1在三阴性乳腺癌 (TNBC) 瘤性和进展中的作用.
- 阐明XBP1对TNBC有所贡献的分子机制.
- 为了确定TNBC的潜在治疗点.
主要方法:
- 利用乳腺癌细胞系模型研究XBP1枯竭的影响.
- 进行了XBP1转录调节网络的全基因组映射.
- 分析了XBP1基因表达特征和与预后相关性的独立患者队列.
主要成果:
- 在TNBC模型中,XBP1耗尽抑制了瘤生长,复发,并减少了TNBC模型中的CD44 (高) CD24 (低) 种群.
- XBP1与HIF1α形成复合体,以调节缺氧诱导因子1α标,推动TNBC瘤性.
- 在TNBC患者中,特定的XBP1基因表达特征与HIF1α/低氧特征和不良预后相关.
结论:
- XBP1在TNBC瘤发生性和进展中发挥着关键作用.
- XBP1-HIF1α转录复合体对于TNBC发育至关重要.
- 准XBP1通路为TNBC提供了一个潜在的治疗策略.
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