线粒体缺陷通过Drosophila的Hippo信号驱动非自主瘤进展
Shizue Ohsawa1, Yoshitaka Sato, Masato Enomoto
1Division of Genetics, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
Nature
|October 2, 2012
概括
线粒体功能障碍和瘤性Ras合作驱动瘤进展. 这涉及到活性氧物种,c-Jun氨基终端激酶 (JNK) 信号传递,以及河马途径,促进转移.
科学领域:
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
- 线粒体生物学 线粒体生物学
背景情况:
- 线粒体呼吸系统功能障碍在人类癌症中很常见.
- 将线粒体功能障碍与瘤进展联系在一起的精确机制尚未完全理解.
研究的目的:
- 调查线粒体功能障碍如何导致瘤进展,特别是与瘤性Ras信号结合.
- 阐明涉及Ras驱动瘤生长和转移的分子途径.
主要方法:
- 利用Drosophila形象上皮作为一个模型系统.
- 研究了活性氧物种 (ROS),c-Jun氨基终端激酶 (JNK) 信号传递和河马通路的作用.
- 研究了Ras激活和 mitochondrial 功能在相邻细胞之间的相互作用.
主要成果:
- 拉斯激活和线粒体功能障碍协同增加反应性氧物种 (ROS) 产量.
- ROS激活JNK信号,该信号与瘤性Ras合作,使Hippo通路失活.
- 这种无活化导致未配对和无翼的上调,促进瘤的进展和转移.
- 拉斯激活细胞中的线粒体功能障碍可以诱导与正常线粒体相邻细胞的转移行为.
结论:
- 线粒体功能障碍和瘤性Ras合作通过ROS/JNK/Hippo途径驱动瘤进展.
- 这项研究为由线粒体缺陷和Ras.驱动的克隆间瘤进展提供了机制性的解释.
- 这些发现强调了线粒体健康在癌症发展和转移中的关键作用.
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