p21-activated kinase 4 regulation of endometrial cancer cell migration and invasion involves the ERK1/2 pathway mediated MMP-2 secretion
p21-activated kinase 4 regulation of endometrial cancer cell migration and invasion involves the ERK1/2 pathway mediated MMP-2 secretion
复制标题
p21激活激酶4对子宫内膜癌细胞迁移和侵袭的调节涉及ERK1/2通路介导的MMP-2分泌
DOI：
10.4149/neo_2013_064
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发表时间：
2013-01-01
期刊：
影响因子：
3
通讯作者：
Wan, X. P.
中科院分区：
文献类型：
--
作者：
Lu, W.;Xia, Y. H.;Wan, X. P.
子宫内膜癌是女性生殖道最常见的恶性肿瘤之一。患有转移性疾病的患者预后不良。然而，到目前为止，EC转移的潜在分子机制在很大程度上是未知的。P21激活激酶4（Pak 4）在细胞运动和肿瘤发生中起重要作用。在这里，我们研究了Pak 4在EC细胞迁移和侵袭中的作用。在多种人EC细胞系中观察到Pak 4过表达。在临床标本中，总Pak 4和磷酸化Pak 4（分别为Pak 4和p-Pak 4）的表达随着EC从正常组织到淋巴结转移的进展而显著增加;两者均与子宫肌层和血管间隙浸润深度、淋巴结转移和组织分化差呈正相关。在两个人EC细胞系中，Pak 4过表达促进细胞的迁移和体外侵袭。短发夹状RNA（shRNA）介导的Pak 4基因的稳定敲低以ERK 1/2-MMP-2依赖的方式抑制EC的转移潜能。这些结果表明Pak 4是EC细胞迁移和侵袭的重要调节因子。因此，Pak 4可能是治疗转移性EC的一个有希望的靶点。
Endometrial cancer (EC) is one of the most common malignancy of the female genital tract. Patients with metastatic disease have a poor prognosis. So far, however, the underlying molecular mechanisms of EC metastasis are largely unknown. P21-activated kinase 4 (Pak4) is important in cell motility and oncogenesis. Here we investigated a role of Pak4 in EC cell migration and invasion. Pak4 overexpression was observed in multiple human EC cell lines. In clinical samples, expression of total and phosphorylated Pak4 (Pak4 and p-Pak4, respectively) increased significantly with progression of EC from normal tissue to lymph node metastasis; both were positively correlated with depth of myometrial and vascular space invasion, lymph nodes metastasis, and poor histological differentiation. In two human EC cell lines, Pak4 overexpression promoted cell migration and invasion in vitro. Short hairpin RNA (shRNA)-mediated stable knockdown of Pak4 inhibited the metastatic potential of EC in an ERK1/2-MMP-2-dependent manner. These results suggest that Pak4 is an important regulator of EC cell migration and invasion. Therefore, Pak4 may be a promising target for the treatment of metastatic EC.