抑制流体I类HDAC可以抑制胰腺癌的进展
Gaoyang Liang1, Tae Gyu Oh1,2, Nasun Hah3
1Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA, 92037, USA.
Nature communications
|December 6, 2023
概括
基因组脱乙酶 (HDACs) 驱动胰腺癌.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 癌症生物学 癌症生物学
- 瘤微环境 瘤微环境
背景情况:
- 胰腺管道腺癌 (PDAC) 具有促进治疗耐药性的脱塑性瘤微环境 (TME).
- 瘤性病变会操纵树叶表观遗传机制,从而产生这种耐药的TME.
研究的目的:
- 为了研究I类组基因脱乙酶 (HDACs) 在调节胰腺 stromal 纤维细胞中的作用.
- 探索HDAC抑制 (HDACi) 在PDAC中的治疗潜力.
主要方法:
- 使用PDAC的小鼠模型.
- 在癌症相关纤维细胞 (CAFs) 中减少HDACs.
- 用 HDAC 抑制剂 氨酸 (Ent) 治疗的 PDAC 模型.
主要成果:
- 第I类HDACs通过SRF和FOXM1.1在胰腺纤维细胞中诱导亲脱质和亲瘤的转录程序.
- 通过LIF表达,HDACs通过LIF表达促进了亲瘤的交叉交叉.
- 在PDAC模型中,CAFs中的HDAC消耗/抑制降低了树皮激活和瘤进展.
- 在PDAC流层中,HDACi丰富了脂原性纤维细胞亚群.
结论:
- 第I类HDACs是PDAC流体的关键表观遗传调节者.
- 准HDACs在表观遗传上调节PDAC层,提供了一个潜在的治疗策略.
- 抑制HDAC通过向树皮组分来抑制PDAC进展,显示出有希望的结果.
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