YAP1功能障碍促进了与乳腺癌易感性相关的分子特性
Tara Fresques1, Jennifer C Lopez2, Deborah Hussey3
1University of the Pacific Stockton, CA United States.
Cancer prevention research (Philadelphia, Pa.)
|December 23, 2025
概括
衰老的乳腺细胞中的YAP1 (Yes-Associated Protein 1) 失调促进了对癌症敏感的状态. 在瘤形成之前,这种早期的分子转移与增加的癌症风险和类似干细胞的特性有关.
科学领域:
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
- 衰老研究研究 衰老研究
背景情况:
- YAP1 (Yes-Associated Protein 1) 是一种与癌症恶性和干细胞特征相关的共转录因子.
- YAP1失调与人类乳腺上皮质的衰老相关,特别是在乳腺上皮细胞,乳腺癌的起源.
- 年龄是乳腺癌的重要风险因素,促使对早期分子事件的研究,从而导致易感性.
研究的目的:
- 调查YAP1失调是否通过诱导癌症易感的细胞状态来促进乳腺癌早期进展.
- 确定YAP1在人类乳腺上皮细胞 (HMEC) 衰老中的作用,涉及癌症风险.
主要方法:
- 根据年龄和遗传癌症风险分层对人类乳腺组织中YAP1表达的分析.
- 培养初级人类乳腺上皮细胞 (HMEC),以评估YAP1表达及其下游标.
- 在衰老后的HMEC中过度表达YAP1,以评估对细胞特性的影响.
主要成果:
- 在老化的人类乳腺组织和培养的HMEC中观察到YAP1表达的增加,以及YAP1转录标的升高.
- 在HMEC中升级的YAP1导致与干细胞命运,端粒酶活性和乳腺癌进展相关的基因表达变化.
- 在静止后的YAP1过度表达HMEC促进了增长潜力和获得干细胞类基因程序的增加.
结论:
- 衰老的有限上皮细胞中的YAP1失调促进了干细胞类状态的采用,有助于癌症易感性.
- 在乳腺癌发育的早期,YAP1可能会通过强加分子状态来增加易感性,从而在瘤形成之前起作用.
- 研究结果表明,YAP1在与衰老相关的乳腺癌风险增加中起着至关重要的作用.
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