PPP3CB Inhibits Migration of G401 Cells via Regulating Epithelial-to-Mesenchymal Transition and Promotes G401 Cells Growth
PPP3CB Inhibits Migration of G401 Cells via Regulating Epithelial-to-Mesenchymal Transition and Promotes G401 Cells Growth
复制标题
PPP3CB 通过调节上皮间质转化抑制 G401 细胞迁移并促进 G401 细胞生长
DOI：
10.3390/ijms20020275
复制
发表时间：
2019-01-02
影响因子：
5.6
通讯作者：
Li, Qianyin
中科院分区：
文献类型：
--
作者：
Chen, Lei;He, Qingling;Li, Qianyin
PPP 3CB属于磷蛋白磷酸酶（PPPs）组。尽管PPP家族的大多数成员在肿瘤细胞的上皮-间质转化（EMT）中发挥重要作用，但PPP 3CB在EMT过程中的功能知之甚少。在此，我们发现PPP 3CB在肾间充质样细胞中的表达高于肾上皮样细胞。PPP 3CB的敲低下调上皮标记物E-cadherin和上调间充质标记物Vimentin，促进细胞状态从上皮向间充质的转变，并重组有助于细胞迁移的肌动蛋白细胞骨架。相反，PPP 3CB过表达逆转EMT并抑制肿瘤细胞的迁移。此外，体外和体内实验表明PPP 3CB的缺失抑制了肿瘤的生长。然而，PPP 3CB的磷酸酶结构域的缺失显示E-钙粘蛋白的表达，迁移和G401细胞增殖没有影响。总之，我们证明PPP 3CB通过调节EMT抑制G401细胞迁移并促进细胞增殖，这两者都与PPP 3CB的磷酸酶活性有关。
PPP3CB belongs to the phosphoprotein phosphatases (PPPs) group. Although the majority of the PPP family play important roles in the epithelial-to-mesenchymal transition (EMT) of tumor cells, little is known about the function of PPP3CB in the EMT process. Here, we found PPP3CB had high expression in kidney mesenchymal-like cells compared with kidney epithelial-like cells. Knock-down of PPP3CB downregulated epithelial marker E-cadherin and upregulated mesenchymal marker Vimentin, promoting the transition of cell states from epithelial to mesenchymal and reorganizing the actin cytoskeleton which contributed to cell migration. Conversely, overexpression of PPP3CB reversed EMT and inhibited migration of tumor cells. Besides, in vitro and in vivo experiments indicated that the loss of PPP3CB suppressed the tumor growth. However, the deletion of the phosphatase domain of PPP3CB showed no effect on the expression of E-cadherin, migration, and G401 cell proliferation. Together, we demonstrate that PPP3CB inhibits G401 cell migration through regulating EMT and promotes cell proliferation, which are both associated with the phosphatase activity of PPP3CB.