Department of General Surgery, Xinhua Hospital, Affiliated to School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
FEBS J. 2013 Jan;280(1):46-55. doi: 10.1111/febs.12048. Epub 2012 Nov 23.
p21-activated kinase (PAK)7 (also known as PAK5) is a member of the group B PAK family of serine/threonine protein kinases, which are effectors of the small GTPases Rac and CDC42. PAK7 can promote neurite outgrowth, induce microtubule stabilization, and activate cell survival signaling pathways. However, the role of PAK7 in cancer is still poorly understood. Here, we showed that PAK7 expression was upregulated in different gastric cancer cell lines and gastric cancer tissues, as compared with human embryonic kidney 293 cells and adjacent normal tissues, respectively. The results suggested that PAK7 expression was related to gastric cancer progression. Thus, we employed lentivirus-mediated small interfering RNA to inhibit PAK7 expression, to investigate the role of PAK7 in human gastric carcinogenesis. RNA interference efficiently downregulated expression of PAK7 in SGC-7901 and MGC-803 cells at both mRNA and protein levels. Knockdown of PAK7 inhibited human gastric cancer cell proliferation by inducing cell cycle arrest in G(0)/G(1) phase, in concordance with the downregulation of CDK2, CDC25A, and cyclin D1. Our data suggest that PAK7 is a new hallmark of gastric cancer, in which PAK7 might contribute to gain of tumor growth potential, acting by affecting the expression of cell cycle regulators. Therefore, PAK7 may be an attractive candidate as a therapeutic target in gastric cancer.
p21 激活激酶 (PAK)7（也称为 PAK5）是丝氨酸/苏氨酸蛋白激酶 B 族 PAK 家族的成员，是小 GTPases Rac 和 CDC42 的效应物。PAK7 可以促进神经突生长、诱导微管稳定，并激活细胞存活信号通路。然而，PAK7 在癌症中的作用仍知之甚少。在这里，我们发现与人类胚胎肾 293 细胞和相邻正常组织相比，PAK7 在不同的胃癌细胞系和胃癌组织中表达上调。结果表明 PAK7 的表达与胃癌的进展有关。因此，我们采用慢病毒介导的小干扰 RNA 抑制 PAK7 的表达，以研究 PAK7 在人类胃癌发生中的作用。RNA 干扰有效地在 SGC-7901 和 MGC-803 细胞中下调 PAK7 的表达，在 mRNA 和蛋白水平上。PAK7 的敲低通过诱导细胞周期停滞在 G0/G1 期，从而抑制人胃癌细胞的增殖，与 CDK2、CDC25A 和细胞周期蛋白 D1 的下调一致。我们的数据表明 PAK7 是胃癌的一个新标志，PAK7 可能通过影响细胞周期调节剂的表达来促进肿瘤生长潜能的获得。因此，PAK7 可能是胃癌治疗的一个有吸引力的候选靶点。
