在前列腺癌中,AR会以不同的方式激活YAP/TAZ
Omar Salem1,2, Siyang Jia1,2, Bin-Zhi Qian3
1The University of Edinburgh, Centre for Inflammation Research, Edinburgh BioQuarter, Edinburgh, UK.
Life science alliance
|June 29, 2023
概括
雄激素通过前列腺癌中的雄激素受体 (AR) 激活YAP/TAZ,影响细胞生长. 向YAP/TAZ或SRF使癌细胞对AR抑制敏感,提供新的治疗策略.
科学领域:
- 细胞生物学 细胞生物学
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- 河马信号通路调节细胞生长,并与癌症有关.
- YAP和TAZ是Hippo通路的关键转录共同调节者,在各种癌症中发挥作用.
- 大多数癌症中YAP/TAZ激活的确切机制尚不清楚.
研究的目的:
- 研究雄激素如何通过前列腺癌中的雄激素受体 (AR) 激活YAP/TAZ.
- 为了阐明AR介导的YAP/TAZ激活的调节机制.
- 探索针对YAP/TAZ和SRF在前列腺癌中的治疗潜力.
主要方法:
- 在前列腺癌细胞中通过AR研究了YAP/TAZ的安卓激活.
- 分析了AR对YAP翻译和TAZ转录 (WWTR1) 的调节.
- 研究了血清响应因子 (SRF) 在AR介导的YAP/TAZ激活中的作用,以及患者数据中与YAP/TAZ基因相关的SRF表达.
主要成果:
- 在前列腺癌中,雄激素通过AR激活YAP/TAZ,对YAP和TAZ进行差异调节.
- AR调节YAP翻译并诱导TAZ (WWTR1) 转录.
- 在前列腺癌患者中,AR介导的YAP/TAZ激活由SRF控制,SRF表达与TAZ和YAP/TAZ基因 (CYR61,CTGF) 相相关.
- YAP/TAZ对AR活性不至关重要,但向它们或SRF使前列腺癌细胞在固独立生长条件下对AR抑制敏感.
结论:
- 剖析了YAP,TAZ和SRF在前列腺癌中的细胞作用.
- 突出了YAP,TAZ和SRF在前列腺瘤发生中的相互作用.
- 建议针对YAP/TAZ或SRF的治疗策略,以增强前列腺癌中AR抑制功效.
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