Chen Peng, Li Kai, Liang Yan, Li Liqing, Zhu Xiaolin
Lung Cancer Medicine Department, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Tianjin, China.
Exp Lung Res. 2013 Feb;39(1):9-17. doi: 10.3109/01902148.2012.744115. Epub 2012 Dec 5.
Novel (nua) kinase family 1 (NUAK1) is a member of the human adenosine monophosphate (AMP)-activated protein kinase family that has been identified as a key tumor cell survival factor. In the present study, we investigated the role of NUAK1 in the migration and invasion of human nonsmall cell lung cancer (NSCLC) cells. Immunohistochemistry staining showed that the expression of NUAK1 correlated with the differentiation and stage of the carcinoma, as well as with lymph node metastasis. Inhibition of NUAK1 expression by small interference RNA severely impaired migration and invasion in A549 cells. In addition, we found that the knockdown of NUAK1 suppressed the expression of MMP-2 and MMP-9 and the activation of NF-kB, which can regulate the transcription of MMP-2 and MMP-9. Correspondingly, NUAK1 knockdown reduced lung metastasis in a xenograft mouse model of NSCLC. Taken together, our results suggest that NUAK1 plays an important role in NSCLC cell migration and invasion.
新型(nua)激酶家族1(NUAK1)是人类单磷酸腺苷(AMP)激活的蛋白激酶家族成员,已被确定为关键的肿瘤细胞存活因子。在本研究中,我们调查了NUAK1在人非小细胞肺癌(NSCLC)细胞迁移和侵袭中的作用。免疫组织化学染色显示,NUAK1的表达与癌的分化、分期以及淋巴结转移相关。小干扰RNA抑制NUAK1表达严重损害了A549细胞的迁移和侵袭。此外,我们发现敲低NUAK1可抑制MMP-2和MMP-9的表达以及NF-κB的激活,而NF-κB可调节MMP-2和MMP-9的转录。相应地,在NSCLC异种移植小鼠模型中,敲低NUAK1可减少肺转移。综上所述,我们的结果表明NUAK1在NSCLC细胞迁移和侵袭中起重要作用。