Han Yingyan, Sun Shujuan, Zhao Meisong, Zhang Zeyu, Gong Song, Gao Peipei, Liu Jia, Zhou Jianfeng, Ma Ding, Gao Qinglei, Wu Peng
Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Dis Markers. 2016;2016:3528064. doi: 10.1155/2016/3528064. Epub 2016 Apr 28.
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.
细胞色素c-1（CYC1）是线粒体复合物III的一个重要亚基。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分析发现，CYC1的高表达与乳腺癌患者的不良预后相关。随后我们证实CYC1在两种高转移性人乳腺癌细胞系中促进转移和增殖。深入研究CYC1的生物学功能，我们发现由于CYC1沉默，线粒体复合物III的活性降低。然后AMP与ATP的比率增加，AMPK被激活。分析其他线粒体复合物的亚基，我们未发现CYC1表达敲低会降低氧化磷酸化任何其他亚基的表达。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在乳腺癌进展中起关键作用，可能是辅助未来患者诊断的一个预测因子。
