Abstract：
Although the p21-activated kinase 2 (PAK2) is an essential serine/threonine protein kinase, its role in lung squamous cell carcinoma (LUSC) progression has yet to be fully understood. We analyzed PAK2 mRNA levels and DNA copy numbers as well as protein levels by quantitative real-time PCR and immunohistochemical staining, respectively, in human LUSC tissues and adjacent normal tissues. Then, we used colony formation assays, cell counting kit-8 assays, matrigel invasion assays, wound healing assays and xenograft models in nude mice to investigate the functions of PAK2 in LUSC progression. We demonstrated that the mRNA levels, DNA copy numbers, and protein levels of PAK2 were up-regulated in human LUSC tissues than in adjacent normal tissues. In addition, a higher PAK2 expression was correlated with a poorer prognosis in LUSC patients. In the in vitro study, we found that PAK2 promoted cell growth, migration, invasion, EMT process, and cell morphology regulation in LUSC cells. Furthermore, PAK2 enhanced tumor cell proliferation, migration, and invasion by regulating actin dynamics through the LIMK1/cofilin signaling. Our findings implicated that the PAK2/LIMK1/cofilin signaling pathway is likely a potential clinical marker and therapeutic target for LUSC.
摘要：
尽管p21激活的激酶2（PAK2）是一种必需的丝氨酸/苏氨酸蛋白激酶，其在肺鳞状细胞癌（LUSC）进展中的作用尚未完全了解。我们通过定量实时PCR和免疫组织化学染色分析了PAK2mRNA水平和DNA拷贝数以及蛋白质水平，分别,在人类LUSC组织和邻近的正常组织中。然后，我们用集落形成试验,细胞计数试剂盒-8测定，基质胶侵入试验，裸鼠伤口愈合试验和异种移植模型研究PAK2在LUSC进展中的功能。我们证明了mRNA水平，DNA拷贝数,人LUSC组织中PAK2的蛋白水平高于邻近的正常组织。此外,在LUSC患者中,较高的PAK2表达与较差的预后相关.在体外研究中，我们发现PAK2促进细胞生长，迁移,入侵,EMT流程,和LUSC细胞的细胞形态调控。此外，PAK2增强肿瘤细胞增殖，迁移,通过LIMK1/cofilin信号调节肌动蛋白动力学和入侵。我们的发现提示PAK2/LIMK1/cofilin信号通路可能是LUSC的潜在临床标志物和治疗靶点。
