Overexpression of P21-activated kinase 4 is associated with poor prognosis in non-small cell lung cancer and promotes migration and invasion.
Overexpression of P21-activated kinase 4 is associated with poor prognosis in non-small cell lung cancer and promotes migration and invasion.
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P21 激活激酶 4 的过度表达与非小细胞肺癌的不良预后相关，并促进迁移和侵袭
DOI：
10.1186/s13046-015-0165-2
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发表时间：
2015-05-15
期刊：
影响因子：
--
通讯作者：
Li L
中科院分区：
文献类型：
--
作者：
Cai S;Ye Z;Wang X;Pan Y;Weng Y;Lao S;Wei H;Li L
P21激活激酶4（PAK4）是Rho家族蛋白Cdc42的效应因子，是一种重要的癌基因，其在许多人类癌症中的表达增加，并且通常与疾病进展和生存率降低呈正相关。然而，对于PAK4在人类非小细胞肺癌（NSCLC）中的表达及生物学功能知之甚少。
通过免疫组织化学、实时定量PCR和蛋白质印迹法评估PAK4在NSCLC组织及相邻非肿瘤组织中的表达。通过卡普兰 - 迈耶分析和考克斯回归评估PAK4表达的预后价值。应用小干扰RNA介导的基因沉默和蛋白激酶测定来证明PAK4在肺癌细胞迁移和侵袭中的作用及机制。
结果显示，PAK4在NSCLC细胞系和人类NSCLC组织中过表达。在体内NSCLC癌细胞的细胞膜和细胞质中均检测到PAK4表达。此外，PAK4表达增加与NSCLC的转移、总生存期缩短和疾病晚期相关。再者，PAK4表达与LIMK1磷酸化表达水平呈正相关。在NSCLC细胞系中敲低PAK4导致LIMK1磷酸化降低，从而使细胞迁移和侵袭减少。此外，PAK4直接与LIMK1结合，并通过磷酸化激活它。
这些数据表明，PAK4介导的LIMK1磷酸化调节NSCLC中的迁移和侵袭。因此，PAK4可能是NSCLC中一个重要的预后标志物和潜在的治疗分子靶点。
BackgroundP21-activated kinase 4 (PAK4), an effector of the Rho family protein Cdc42, is an important oncogene whose expression is increased in many human cancers and is generally positively correlated with advanced disease and decreased survival. However, little is known about the expression and biological function of PAK4 in human non-small cell lung cancer (NSCLC).MethodsPAK4 expression in NSCLC tissues and adjacent non-tumor tissues were assessed by immunohistochemistry, real-time PCR, and western blotting. Prognostic value of PAK4 expression was evaluated by Kaplan-Meier analysis and Cox regression. siRNA-mediated gene silencing and protein kinase assay was applied to demonstrate the role and the mechanism of PAK4 in lung cancer cell migration, invasion.ResultsThe results showed that PAK4 was overexpressed in NSCLC cell lines and human NSCLC tissues. PAK4 expression was detected both in the membranes and cytoplasm of NSCLC cancer cells in vivo. Moreover, increased expression of PAK4 was associated with metastasis, shorter overall survival, advanced stage of NSCLC. Furthermore, PAK4 expression was positively correlated with phosphorylation of LIMK1 expression levels. Knockdown of PAK4 in NSCLC cell lines led to reduce the phosphorylation of LIMK1, which resulted in decrease of the cell migration and invasion. In addition, PAK4 bound to LIMK1 directly and activated it via phosphorylation.ConclusionsThese data demonstrate that PAK4 mediated LIMK1 phosphorylation regulates the migration and invasion in NSCLC. Therefore, PAK4 might be a significant prognostic marker and potential therapeutic molecular target in NSCLC.
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影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
Thun, Michael J.
影响因子：
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作者：
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影响因子：
37.3
作者：
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通讯作者：
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影响因子：
11.4
作者：
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通讯作者：
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影响因子：
3
作者：
Lu, W.;Xia, Y. H.;Wan, X. P.
通讯作者：
Wan, X. P.