The role of CDK1 in apoptin-induced apoptosis in hepatocellular carcinoma cells.
The role of CDK1 in apoptin-induced apoptosis in hepatocellular carcinoma cells.
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DOI：
10.3892/or.2013.2426
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发表时间：
2013-07
期刊：
影响因子：
4.2
通讯作者：
Jing Zhao;Suxia Han;Jin-lu Ma;X. Ying;Peijun Liu;Juan Li;Lijuan Wang;Ying Zhang;Jiguang Ma;Li Zhang;Qing Zhu
中科院分区：
文献类型：
--
作者：
Jing Zhao;Suxia Han;Jin-lu Ma;X. Ying;Peijun Liu;Juan Li;Lijuan Wang;Ying Zhang;Jiguang Ma;Li Zhang;Qing Zhu
Apoptin是一种从鸡贫血病毒中提取的小蛋白，它能特异性地诱导转化细胞或肿瘤细胞的凋亡，而不能诱导正常细胞的凋亡。因此，凋亡素参与了一个一般的、肿瘤特异性的途径。凋亡素诱导的细胞凋亡可能需要额外的相互作用伙伴来激活癌细胞中的特定信号通路。许多分子与凋亡素相互作用，并在凋亡素的核定位或其肿瘤选择性细胞毒性中发挥重要作用。我们的数据表明，凋亡素选择性地杀死HepG2肝细胞癌（HCC）细胞，但对正常肝细胞系HL-7702没有影响。对人类HCC组织样本的分析证实，CDK1（细胞周期蛋白依赖性激酶1）活性在原发性恶性肿瘤中检测到，但在健康的副肿瘤组织中未检测到。shRNA敲低CDK1可显著降低凋亡素的肿瘤特异性杀伤作用，提示CDK1在调节凋亡素诱导的细胞凋亡中发挥重要作用。此外，在敲低CDK1后，大多数凋亡素从细胞核转移到细胞质中。总之，我们的研究结果首次揭示了凋亡素在复杂的肿瘤发生过程中与CDK1相互作用。CDK1与凋亡素之间的联系可能是调节肿瘤细胞凋亡的一种新的细胞信号通路；因此，细胞凋亡素可能具有直接用于癌症治疗的药理潜力。
Apoptin, a small protein derived from the chicken anemia virus, specifically induces apoptosis in transformed cells or tumor cells but not in normal cells. Thus, apoptin is involved in a general, tumor-specific pathway. Apoptin-induced apoptosis presumably requires additional interaction partners that activate specific signaling pathways in cancer cells. A number of molecules interact with apoptin and play an important role in the nuclear localization of apoptin or its tumor-selective cytotoxicity. Our data indicated that apoptin selectively kills HepG2 hepatocellular carcinoma (HCC) cells but has no effect on the normal liver cell line HL-7702. Analyses of human HCC tissue samples confirmed that CDK1 (cyclin-dependent kinase 1) activity was detected in primary malignancies but not in healthy paraneoplastic tissues. shRNA knockdown of CDK1 significantly reduced the tumor-specific killing effects of apoptin, suggesting that CDK1 plays an important role in the regulation of apoptin-induced apoptosis. Furthermore, the majority of apoptin translocated to the cytoplasm from the nucleus after knockdown of CDK1. Collectively, our results revealed for the first time that apoptin interacts with CDK1 in the complex process of tumorigenesis. The link between CDK1 and apoptin may be a novel cellular signaling pathway to modulate apoptosis in cancer; therefore, apoptin may have pharmacological potential to be directly employed for cancer therapy.