Wang Congcong, Wang Junyan, Xu Ruifeng, Huang Xia, Li Qiushuang, Zhang Chenxi, Yuan Baiyin
College of Life and Health Sciences, Wuhan University of Science and Technology, Wuhan, Hubei 430081, China.
Central Laboratory, Nanjing Chest Hospital, Affiliated Nanjing Brain Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China.
J Biomed Res. 2024 May 25;39(2):1-14. doi: 10.7555/JBR.37.20230317.
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 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 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.
尽管p21激活激酶2(PAK2)是一种重要的丝氨酸/苏氨酸蛋白激酶,但其在肺鳞状细胞癌(LUSC)进展中的作用尚未完全明确。我们分别通过定量实时PCR和免疫组化染色分析了人LUSC组织及相邻正常组织中的mRNA水平、DNA拷贝数以及蛋白水平。然后,我们使用集落形成实验、细胞计数试剂盒-8实验、基质胶侵袭实验、伤口愈合实验以及裸鼠异种移植模型来研究PAK2在LUSC进展中的功能。我们证明,与相邻正常组织相比,人LUSC组织中PAK2的mRNA水平、DNA拷贝数和蛋白水平均上调。此外,PAK2表达较高与LUSC患者预后较差相关。在本研究中,我们发现PAK2促进LUSC细胞的生长、迁移、侵袭、上皮-间质转化过程以及细胞形态调控。此外,PAK2通过LIMK1/丝切蛋白信号通路调节肌动蛋白动力学,从而增强肿瘤细胞的增殖、迁移和侵袭。我们的研究结果表明,PAK2/LIMK1/丝切蛋白信号通路可能是LUSC潜在的临床标志物和治疗靶点。