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肺腺癌远距离重新连接肝脏循环稳定

Selma Masri¹, Thales Papagiannakopoulos², Kenichiro Kinouchi¹

¹Center for Epigenetics and Metabolism, INSERM Unit 904, Department of Biological Chemistry, University of California, Irvine (UCI), Irvine, CA 92697, USA.

|May 7, 2016

概括

肺腺癌会改变肝脏的新陈代谢而不会影响核心的生理时钟. 这种癌症作为内生昼夜组织者, 重新编程肝脏通路并影响葡萄糖和脂质代谢.

科学领域:

时间生物学
癌症生物学
代谢调节

背景情况:

生物钟调节生理过程并适应环境信号.
组织特异性病理对全身昼夜节律的影响在很大程度上是未知的.
对于生物医学研究来说, 了解生物节律中器官之间的沟通至关重要.

研究的目的:

研究肺腺癌如何影响远端组织的昼夜新陈代谢.
确定癌症破坏全身昼夜平衡的分子机制.
确定癌症是否可以作为内源性昼夜调节器.

主要方法:

在携带瘤的小鼠中高通量转录组和代谢组.
对肝脏组织进行分子和代谢变化的分析.
研究STAT3-Socs3炎症通路及其对AKT,AMPK和SREBP等信号通路的下游影响.

主要成果:

肺腺癌诱导肝脏中独特的循环转录和代谢物签名.
癌症并没有改变肝脏的生理时钟, 而是重编程代谢功能.
通过涉及STAT3-Socs3途径的促炎反应破坏肝脏代谢,影响胰岛素,葡萄糖和脂质代谢.

结论:

肺腺癌作为一个强大的内源性昼夜调节器 (ECO).
它们可以重新连接远端器官的病理生理学,
这项研究揭示了癌症引起的新陈代谢失调的器官间通信机制.

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