CYC1 Predicts Poor Prognosis in Patients with Breast Cancer.

CYC1 Predicts Poor Prognosis in Patients with Breast Cancer.
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CYC1 预测乳腺癌患者预后不良

DOI:
10.1155/2016/3528064
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发表时间:
2016
期刊:
影响因子:
--
通讯作者:
Wu P
Wu P
中科院分区:
医学4区
文献类型:
--
作者:
Han Y;Sun S;Zhao M;Zhang Z;Gong S;Gao P;Liu J;Zhou J;Ma D;Gao Q;Wu P

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细胞色素 c-1 (CYC1) 是线粒体复合物 III 的重要亚基。然而,其在肿瘤进展中的作用尚不清楚。我们发现CYC1在乳腺肿瘤组织中表达上调,尤其是在有淋巴结转移的组织中。使用在线数据库和工具,CYC1 的较高表达与乳腺癌患者的不良预后相关。然后我们证实 CYC1 有助于两种高度转移的人乳腺癌细胞系的转移和增殖。深入研究CYC1的生物学功能,我们发现由于CYC1的沉默,线粒体复合物III的活性降低。然后AMP与ATP的比率增加并且AMPK被激活。分析其他线粒体复合物的单位,我们没有发现 CYC1 表达的敲低会降低任何其他 OXPHOS 单位的表达。我们得出结论,CYC1 通过抑制 AMPK 的激活促进肿瘤转移,并通过促进 ATP 的产生促进肿瘤生长。我们的结果表明 CYC1 在乳腺癌进展中发挥着至关重要的作用,并且可能是帮助未来患者诊断的预测因素。
Cytochrome c-1 (CYC1) is an important subunit of mitochondrial complex III. However, its role in tumor progression is unclear. We found that CYC1 was upregulated in breast tumor tissues, especially in tissues with lymph node metastasis. And higher expression of CYC1 correlates with poor prognosis in breast cancer patients using online databases and tools. Then we confirmed that CYC1 contributed to metastasis and proliferation in two highly metastatic human breast cancer cell lines. Digging into the biological function of CYC1, we found the activity of mitochondrial complex III decreased due to silencing CYC1. Then the ratio of AMP to ATP increased and AMPK was activated. Analyzing units of other mitochondrial complexes, we did not find knockdown of CYC1 expression reduced expression of any other unit of OXPHOS. We concluded that CYC1 promoted tumor metastasis via suppressing activation of AMPK and contributed to tumor growth via facilitating production of ATP. Our results indicated that CYC1 plays crucial roles in breast cancer progression and might be a predictive factor assisting future patient diagnosis.