摘要
线粒体是一个动态的细胞器,在整合细胞信号中发挥关键作用。在肿瘤形成的各个阶段都可以见到明显的线粒体改变,靶向线粒体通路已成为一种新的抗癌治疗策略。Wnt信号通路调节着许多基本的细胞功能,如增殖、存活、迁移、干细胞维持以及线粒体代谢和动力学。最新证据表明,线粒体诱导的Wnt信号调控是影响细胞命运决定的一种新机制。线粒体与Wnt信号通路之间的相互作用表现为一个前馈环,Wnt激活后调节线粒体功能,继而又进一步驱动Wnt信号通路。在本文中,我们将讨论线粒体主导的Wnt信号调控及其在肿瘤形成和抗癌治疗中的意义。
Mitochondria are dynamic organelles that play a key role in integrating cellular signaling.Mitochondrial alterations are evident in all stages of tumorigenesis and targeting mitochondrial pathways has emerged as an anticancer therapeutic strategy.The Wnt-signaling pathway regulates many fundamental cellular functions such as proliferation,survival,migration,stem-cell maintenance,and mitochondrial metabolismand dynamics.Emerging evidence demonstrates that mitochondrial-induced regulation of Wnt signaling provides an additional mechanism to influence cell-fate decisions.Crosstalk between mitochondria and Wnt signaling presents a feedforward loop in which Wnt activation regulates mitochondrial function that,in turn,drives Wnt signaling.In this mini-review,we will discuss the recent evidence revealing the mitochondrial control of Wnt signaling and its implications for tumorigenesis and anticancer therapeutic targeting.
基金
supported by National Institutes of Health grant R01-DK117001(to A.L.T.)
Litwin IBD Pioneers Crohn’s Colitis Foundation 391869(to A.L.T.).