STYK1 promotes tumor growth and metastasis by reducing SPINT2/HAI-2 expression in non-small cell lung cancer
STYK1 promotes tumor growth and metastasis by reducing SPINT2/HAI-2 expression in non-small cell lung cancer
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STYK1通过降低非小细胞肺癌中SPINT2/HAI-2的表达促进肿瘤生长和转移
DOI：
10.1038/s41419-019-1659-1
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发表时间：
2019-06-04
影响因子：
9
通讯作者：
Yan, Xiaolong
中科院分区：
文献类型：
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作者：
Ma, Zhiqiang;Liu, Dong;Yan, Xiaolong
非小细胞肺癌（NSCLC）是全球癌症死亡的主要原因。然而，NSCLC进展的分子机制仍不完全清楚。在这项研究中，招募了347例具有完整临床病理特征的接受NSCLC手术的患者进行研究。我们证实，丝氨酸苏氨酸酪氨酸激酶1（STYK 1）表达升高或丝氨酸肽酶抑制剂Kunitz 2型（SPINT 2/HAI-2）表达降低与NSCLC患者的不良预后、肿瘤浸润和转移显著相关。STYK 1过表达促进NSCLC细胞增殖、迁移和侵袭。STYK 1还通过E-cadherin下调和Snail上调诱导上皮-间质转化。此外，RNA-seq、定量聚合酶链反应（qRT-PCR）和蛋白质印迹分析证实，STYK 1过表达显著降低了NSCLC细胞中SPINT 2的水平，SPINT 2过表达在体外和体内均明显逆转了STYK 1介导的NSCLC进展。进一步生存分析显示STYK 1高表达和SPINT 2低表达的NSCLC患者预后和生存率最差。这些结果表明STYK 1通过降低SPINT 2表达促进NSCLC进展。因此，靶向STYK 1和SPINT 2可能是NSCLC的一种新的治疗策略。
Non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths worldwide. However, the molecular mechanisms underlying NSCLC progression remains not fully understood. In this study, 347 patients with complete clinicopathologic characteristics who underwent NSCLC surgery were recruited for the investigation. We verified that elevated serine threonine tyrosine kinase 1 (STYK1) or decreased serine peptidase inhibitor Kunitz type 2 (SPINT2/HAI-2) expression significantly correlated with poor prognosis, tumor invasion, and metastasis of NSCLC patients. STYK1 overexpression promoted NSCLC cells proliferation, migration, and invasion. STYK1 also induced epithelial–mesenchymal transition by E-cadherin downregulation and Snail upregulation. Moreover, RNA-seq, quantitative polymerase chain reaction (qRT-PCR), and western blot analyses confirmed that STYK1 overexpression significantly decreased the SPINT2 level in NSCLC cells, and SPINT2 overexpression obviously reversed STYK1-mediated NSCLC progression both in vitro and in vivo. Further survival analyses showed that NSCLC patients with high STYK1 level and low SPINT2 level had the worst prognosis and survival. These results indicated that STYK1 facilitated NSCLC progression via reducing SPINT2 expression. Therefore, targeting STYK1 and SPINT2 may be a novel therapeutic strategy for NSCLC.