在荷尔蒙阳性乳腺癌中,HDAC抑制剂调节Hippo通路信号传递
Ting-I Lin1,2, Yi-Ru Tseng1,2, Min-Jyun Dong1,2
1Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan.
Clinical epigenetics
|February 26, 2025
概括
基因组脱乙酶抑制剂 (HDACi) 影响YAP表达并激活激素受体阳性乳腺癌中的Hippo通路基因. 上调的CCDC80和GADD45A与这些患者的更好的生存相关.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 激素受体阳性 (HR+),HER2阴性乳腺癌是最常见的亚型.
- 基因组脱乙酶抑制剂 (HDACi) 在HR+乳腺癌中显示出临床益处.
- 涉及YAP/TAZ的Hippo通路在癌症中起着复杂的作用,YAP在HR+乳腺癌中起着瘤抑制作用.
研究的目的:
- 为了研究HDAC抑制剂与HR+乳腺癌中的Hippo途径之间的联系.
- 为了确定HDACi活动的新型分子机制和患者生存的潜在生物标志物.
主要方法:
- 研究了HDACi对YAP表达和Hippo通路基因转录的影响.
- 鉴定并验证了由HDACi.Ci升调的Hippo通路基因.
- 在HR+乳腺癌队列 (METABRIC) 和泛癌分析 (TCGA) 中分析了基因表达和生存数据.
主要成果:
- HDACi治疗降低了YAP表达的调节,但激活了TEAD介导的转录程序,从而调节了正规的Hippo通路基因.
- 鉴定出CCDC80,GADD45A,F3和TGFB2是HDACi上调的基因,与HR+乳腺癌的存活率提高有关.
- 在多种癌症类型的瘤组织中观察到较低的CCDC80和GADD45A表达,包括乳腺癌.
- 高CCDC80和/或GADD45A表达与HR+乳腺癌患者的更好的生存结果显著相关.
结论:
- HDACi诱导YAP下调并激活特定的Hippo通路基因,为其临床活动提供了一种新的机制.
- CCDC80和GADD45A是提高激素受体阳性乳腺癌生存率的潜在生物标志物.
- 对CCDC80和GADD45A作用的进一步研究可能会揭示HR+乳腺癌的新治疗策略.
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