分子伴侣CCT3支持肝癌细胞中正常的有丝分裂进程和细胞增殖。
Molecular chaperone CCT3 supports proper mitotic progression and cell proliferation in hepatocellular carcinoma cells.
作者信息
Zhang Yuanyuan, Wang Yuqi, Wei Youheng, Wu Jiaxue, Zhang Pingzhao, Shen Suqin, Saiyin Hexige, Wumaier Reziya, Yang Xianmei, Wang Chenji, Yu Long
机构信息
State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, 2005 Songhu Road, Shanghai 200433, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China.
State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, 2005 Songhu Road, Shanghai 200433, China.
出版信息
Cancer Lett. 2016 Mar 1;372(1):101-9. doi: 10.1016/j.canlet.2015.12.029. Epub 2015 Dec 29.
CCT3 was one of the subunits of molecular chaperone CCT/TRiC complex, which plays a central role in maintaining cellular proteostasis. We demonstrated that expressions of CCT3 mRNA and protein are highly up-regulated in hepatocellular carcinoma (HCC) tissues, and high level of CCT3 is correlated with poor survival in cancer patients. In HCC cell lines, CCT3 depletion suppresses cell proliferation by inducing mitotic arrest at prometaphase and apoptosis eventually. We also identified CCT3 as a novel regulator of spindle integrity and as a requirement for proper kinetochore-microtubule attachment during mitosis. Moreover, we found that CCT3 depletion sensitizes HCC cells to microtubule destabilizing drug Vincristine. Collectively, our study suggests that CCT3 is indispensible for HCC cell proliferation, and provides a potential drug target for treatment of HCC.
CCT3是分子伴侣CCT/TRiC复合体的亚基之一，在维持细胞蛋白质稳态中起核心作用。我们证明，CCT3 mRNA和蛋白质的表达在肝细胞癌（HCC）组织中高度上调，并且CCT3的高水平与癌症患者的不良生存相关。在HCC细胞系中，CCT3缺失通过诱导有丝分裂前期的有丝分裂停滞并最终导致细胞凋亡来抑制细胞增殖。我们还确定CCT3是纺锤体完整性的新型调节因子，并且是有丝分裂期间正确的动粒-微管附着所必需的。此外，我们发现CCT3缺失使HCC细胞对微管破坏药物长春新碱敏感。总的来说，我们的研究表明CCT3对HCC细胞增殖是不可或缺的，并为HCC治疗提供了潜在的药物靶点。
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