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通过YAP限制肠道干细胞扩张和再生反应
Evan R Barry1, Teppei Morikawa, Brian L Butler
1Stem Cell Program and Department of Hematology/Oncology, Children's Hospital, Boston, Massachusetts 02115, USA.
Nature
|November 27, 2012
概括
是的相关蛋白1 (YAP) 通过限制Wnt信号,在肠道再生期间意外地抑制生长. 失去YAP会导致过敏,导致增生和微腺瘤,对结直肠癌治疗有影响.
科学领域:
- 细胞生物学 细胞生物学
- 发育生物学 发展生物学
- 在瘤学瘤学.
背景情况:
- Wnt信号通路驱动肠道的自我更新和再生.
- 在再生过程中控制Wnt驱动的扩散的机制尚未完全理解.
研究的目的:
- 为了研究yes相关蛋白1 (YAP) 在调节肠道再生期间的Wnt信号传递中的作用.
- 阐明YAP控制增殖的机制及其对结直肠癌的影响.
主要方法:
- 利用老鼠和人类模型研究肠道再生.
- 在YAP中使用了转基因表达和基因损失模型.
- 研究了YAP与Wnt路径组件的相互作用,包括混乱的 (DVL).
- 分析了YAP在人类结直肠癌中的表达,并测试了YAP对瘤外移植的影响.
主要成果:
- YAP表现出一种抑制生长的功能,限制了Wnt基因表达和肠道密码.
- 失去YAP会导致Wnt过敏,增生,干细胞扩张和微腺瘤形成.
- 细胞质YAP通过限制DVL核转移来限制Wnt信号传输.
- YAP沉默与人类侵袭性结直肠癌相关,YAP表达抑制了瘤异种植的生长.
结论:
- 在再生组织中,YAP作为Wnt驱动的增殖的新型平衡作用.
- YAP的增长抑制作用为结直肠恶性瘤提供了潜在的治疗点.
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