Inhibition of kinesin family member 20B sensitizes hepatocellular carcinoma cell to microtubule-targeting agents by blocking cytokinesis.
Inhibition of kinesin family member 20B sensitizes hepatocellular carcinoma cell to microtubule-targeting agents by blocking cytokinesis.
复制标题
抑制驱动蛋白家族成员 20B 通过阻断胞质分裂使肝细胞癌细胞对微管靶向药物敏感
DOI：
10.1111/cas.13794
复制
发表时间：
2018-11
期刊：
影响因子：
5.7
通讯作者：
Huang K
中科院分区：
文献类型：
--
作者：
Liu X;Li Y;Zhang X;Liu XY;Peng A;Chen Y;Meng L;Chen H;Zhang Y;Miao X;Zheng L;Huang K
驱动蛋白家族成员20 B（KIF 20 B，也称为MPHOSPH 1）是一种在胞质分裂中起关键作用的驱动蛋白。以前，我们和其他人已经证明了KIF 20 B在几种癌症中的致癌作用;然而，其致瘤作用的确切机制仍不清楚。在此，我们发现KIF 20 B在人肝细胞癌（HCC）中过表达，并报道了KIF 20 B水平与患者预后呈负相关。从机制上讲，减少KIF 20 B以纺锤体组装检查点独立的方式在末期阻断HCC细胞的有丝分裂退出。重要的是，减少KIF 20 B与三种微管相关药物（MTA）协同作用，以p53或p14 ARF依赖性抑制p53-wt或p53-null HCC细胞。除紫杉醇外，减少KIF 20 B也增强了两种化疗药物羟基喜树碱和丝裂霉素C的毒性。总之，我们发现了一种新的机制，即通过抑制KIF 20 B来阻断胞质分裂增加了MTA的疗效;因此，我们的结果表明，通过将MTA与KIF 20 B抑制相结合，同时阻断中期和末期的有丝分裂，可以实现针对HCC的双重有丝分裂抑制方法。
Kinesin family member 20B (KIF20B, also known as MPHOSPH1) is a kinesin protein that plays a critical role in cytokinesis. Previously, we and others have demonstrated the oncogenic role of KIF20B in several cancers; however, the exact mechanisms underlying its tumorigenic effects remain unclear. Herein, we showed overexpression of KIF20B in human hepatocellular carcinoma (HCC) and reported a negative correlation between KIF20B level and prognosis of patients. Mechanistically, reducing KIF20B blockades mitotic exit of HCC cells at telophase in a spindle assembly checkpoint independent way. Importantly, reducing KIF20B acts synergistically with three microtubule‐associated agents (MTA) to p53‐ or p14ARF‐dependently suppress p53‐wt or p53‐null HCC cells. In addition to taxol, reducing KIF20B also enhanced the toxicity of two chemotherapeutic drugs, hydroxycamptothecin and mitomycin C. In conclusion, we found a novel mechanism in that blocking cytokinesis by KIF20B inhibition increases the efficacy of MTA; our results thus suggested a dual‐mitotic suppression approach against HCC by combining MTA with KIF20B inhibition, which simultaneously blocks mitosis at both metaphase and telophase.
登录
查看更多内容
影响因子：
25.7
作者：
Derdak, Zoltan;Villegas, Kristine A.;Harb, Ragheb;Wu, Annie M.;Sousa, Aryanna;Wands, Jack R.
通讯作者：
Wands, Jack R.
影响因子：
8.8
作者：
Forys JT;Kuzmicki CE;Saporita AJ;Winkeler CL;Maggi LB Jr;Weber JD
通讯作者：
Weber JD
影响因子：
20.3
作者：
Karp, Judith E.;Smith, B. Douglas;Rudek, Michelle A.
通讯作者：
Rudek, Michelle A.
MPHOSPH1：肝细胞癌的潜在治疗靶点
影响因子：
11.2
作者：
Liu, Xinran;Zhou, Yafan;Huang, Kun
通讯作者：
Huang, Kun
影响因子：
5.8
作者：
Kuo, Tzu-Ching;Lu, Hsing-Pang;Chao, Chuck C. -K.
通讯作者：
Chao, Chuck C. -K.