葡萄糖的积累和相隔驱动肝脏瘤的开始
Qingxu Liu1, Jiaxin Li1, Weiji Zhang1
1State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.
Cell
|October 22, 2021
概括
肝癌始于糖原的积累, 不仅仅是葡萄糖的使用. 这种过程将Hippo激酶隔离,促进Yap活动和瘤生长. 减少糖原储存可以阻止肝癌的进展.
科学领域:
- 生物化学
- 癌症学
- 细胞生物学
背景情况:
- 瘤细胞通常会增加葡萄糖的消耗.
- 葡萄糖储存的一种形式 - - 葡萄糖积累被认为是肝癌发展的关键早期事件.
研究的目的:
- 研究葡萄糖在肝脏恶性转变中的作用.
- 阐明糖原影响肝脏瘤发生的分子机制.
主要方法:
- 在前恶性和恶性肝细胞中分析葡萄糖-6-酸酶 (G6PC) 和肝糖原酸酶 (PYGL).
- 研究糖原的物理特性及其与拉福林-Mst1/2复合物和Hippo激酶的相互作用.
- 使用G6PC或PYGL缺乏的小鼠模型,评估依赖于Yap的肝脏生长和瘤发生.
主要成果:
- 降低G6PC的调节促进了前恶性肝细胞的葡萄糖储存和糖原积累.
- 累积的糖原经历液-液相分离,隔离Hippo激酶 (Mst1/2) 并缓解Yap抑制.
- 在人类和小鼠中,G6PC或PYGL缺乏导致糖原储存疾病,肝脏膨胀和依赖于Yap的瘤形成.
- 消除糖原的积累可以防止肝脏的生长和癌症,而增加的储存可以加速肝脏的生长.
结论:
- 癌症发起细胞采用糖原储存表型.
- 通过隔离激酶抑制Hippo信号,从而促进Yap活动.
- 针对葡萄糖代谢或其相分离特性可能为肝癌提供新的治疗策略.
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