Mitochondrial fission forms a positive feedback loop with cytosolic calcium signaling pathway to promote autophagy in hepatocellular carcinoma cells
Mitochondrial fission forms a positive feedback loop with cytosolic calcium signaling pathway to promote autophagy in hepatocellular carcinoma cells
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线粒体分裂与胞浆钙信号通路形成正反馈环促进肝癌细胞自噬
DOI：
10.1016/j.canlet.2017.05.034
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发表时间：
2017-09-10
期刊：
影响因子：
9.7
通讯作者：
Xing, Jinliang
中科院分区：
文献类型：
--
作者：
Huang, Qichao;Cao, Haiyan;Xing, Jinliang
线粒体形态和胞质钙[Ca2+] C的水平都被主动改变并在许多恶性肿瘤中起关键作用。但是，这两个过程之间是否存在巧妙地控制恶性表型的通信远非清晰。我们研究了人肝细胞癌（HCC）细胞中线粒体裂变和胞质钙信号传导之间的相互调节。此外，还探索了潜在的分子机制和对自噬的协同作用。我们的结果表明，线粒体裂变增加了[Ca2+] C和HCC细胞中钙振荡。我们进一步发现，线粒体裂变介导的钙信号传导取决于ROS激活的NF-kappa B途径，这促进了STIM1的表达和随后的商店经营钙的钙。此外，我们还证明，[Ca2+] C的增加分别通过转录因子NFATC2和C-MYC的上调表达来促进线粒体裂变。此外，阳性反馈回路显着促进了Ca2+/camkk/ampk途径的HCC细胞全球自噬。我们的数据表明，线粒体裂变和胞质钙信号传导之间的反馈回路及其在HCC细胞自噬中的促进作用，这为该环提供了证据，作为肿瘤治疗中潜在的药物靶标。 （c）2017 Elsevier B.V.保留所有权利。
Both mitochondrial morphology and the level of cytosolic calcium [Ca2+]c are actively changed and play critical roles in a number of malignancies. However, whether communications existed between these two processes to ingeniously control the malignant phenotype are far from clear. We investigated the reciprocal regulation between mitochondrial fission and cytosolic calcium signaling in human hepatocellular carcinoma (HCC) cells. Furthermore, the underlying molecular mechanisms and the synergistic effect on autophagy were explored. Our results showed that mitochondrial fission increased the [[Ca2+]c and calcium oscillation in HCC cells. We further found that mitochondrial fission -mediated calcium signaling was dependent on ROS-activated NF-kappa B pathways, which facilitated the expression of STIM1 and subsequent store-operated calciumentry. Additionally, we also demonstrated that increase in [Ca2+]c promoted mitochondrial fission by up-regulating expression of Drpl and FIS1 via transcription factors NFATC2 and c-Myc, respectively. Moreover, the positive feedback loop significantly promoted HCC cell global autophagy by Ca2+/CAMKK/AMPK pathway. Our data demonstrate a positive feedback loop between mitochondrial fission and cytosolic calcium signaling and their promoting role in autophagy of HCC cells, which provides evidence for this loop as a potential drug target in tumor treatment. (C) 2017 Elsevier B.V. All rights reserved.