Overexpression of NIMA-related kinase 6 (NEK6) contributes to malignant growth and dismal prognosis in Human Breast Cancer
Overexpression of NIMA-related kinase 6 (NEK6) contributes to malignant growth and dismal prognosis in Human Breast Cancer
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NIMA 相关激酶 6 (NEK6) 的过度表达导致人类乳腺癌恶性生长和不良预后
DOI：
10.1016/j.prp.2018.07.030
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发表时间：
2018-10-01
影响因子：
2.8
通讯作者：
Shao, Zhimin
中科院分区：
文献类型：
--
作者：
He, Zhixian;Ni, Xiaojian;Shao, Zhimin
NIMA相关激酶6（Nek 6）是一种蛋白激酶，参与多种细胞过程，包括细胞周期调节、凋亡、衰老、端粒延长和化学抗性。在本研究中，我们研究了Nek 6在乳腺肿瘤发生中的作用以及Nek 6在乳腺癌中表达的预后价值。免疫组化和Western blot分析，以确定Nek 6在133例乳腺癌标本中的表达谱。与邻近的非肿瘤组织相比，Nek 6在大多数乳腺癌标本中过表达。此外，我们发现Nek 6的高表达与乳腺癌的组织学分级、肿瘤大小和TNM分期有关。线性回归分析显示Nek 6和Ki-67水平之间存在显著相关性。考克斯回归分析显示Nek 6表达是乳腺癌独立的预后预测因子。此外，在MCF-7细胞中，随着血清饥饿的释放，细胞内Nek 6的水平显著增加。EdU掺入实验表明，Nek 6的缺失明显抑制MCF-7细胞的增殖。最后，球状体形成试验显示，Nek 6的干扰导致乳腺癌细胞的六钩蚴形成能力降低。总之，我们的研究结果表明，Nek 6在乳腺癌细胞增殖中起着促进作用，并可能作为一个有前途的乳腺癌治疗靶点。
NIMA Related Kinase 6 (Nek6) is a protein kinase involved in various cellular processes, including cell cycle regulation, apopotosis, senescence, telomere maintainance and chemoresistance. In the present study, we investigated the role of Nek6 in breast tumorigenesis and the prognostic merit of Nek6 expression in breast cancer. Immunohistochemistry and Western blot analyses was conducted to determine the expression profile of Nek6 in 133 breast cancer specimens. Nek6 was overexpressed in a majority of breast cancer specimens, compared with the adjacent non-tumorous tissues. Furthermore, we revealed that high expression of Nek6 was associated with histologic grade, tumor size and TNM stage in breast cancer. Liner regression analysis showed a significant association between the levels of Nek6 and Ki-67. Cox regression analysis indicated that Nek6 expression was an independent prognostic predictor for breast cancer. Moreover, intracellular level of Nek6 was remarkably increased following the release from serum starvation in MCF-7 cells. EdU incorporation assay indicated that depletion of Nek6 remarkably impaired the proliferation of MCF-7 cells. Finally, spheroid formation assay revealed that interference of Nek6 led to diminished oncospheroid-forming capacity of breast cancer cells. In conclusion, our results imply that Nek6 plays a facilitating role in breast cancer cell proliferation and may serve as a promising therapeutic target for breast cancer.