Proepithelin promotes migration and invasion of 5637 bladder cancer cells through the activation of ERK1/2 and the formation of a paxillin/FAK/ERK complex
Proepithelin promotes migration and invasion of 5637 bladder cancer cells through the activation of ERK1/2 and the formation of a paxillin/FAK/ERK complex
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DOI：
10.1158/0008-5472.can-06-0633
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发表时间：
2006-07-15
期刊：
影响因子：
11.2
通讯作者：
Morrione, Andrea
中科院分区：
文献类型：
--
作者：
Monami, Giada;Gonzalez, Eva M.;Morrione, Andrea
生长因子前上皮素（也称为颗粒蛋白前体、顶粒蛋白、PC衍生生长因子或颗粒蛋白-上皮素前体）是一种分泌型糖蛋白，作为细胞生长、迁移和转化的重要调节因子发挥作用。上皮素原在乳腺癌、卵巢癌和肾癌以及胶质母细胞瘤的多种癌细胞系和临床标本中过表达。在这项研究中，我们研究了pepithelin对膀胱癌细胞使用人重组pepithelin纯化到同质293-EBNA细胞的影响。虽然proepithelin并没有明显影响细胞生长，它促进迁移的5637膀胱癌细胞和刺激在体外伤口闭合和侵袭。这些作用需要激活促分裂原活化蛋白激酶途径和桩蛋白，其在前上皮素刺激后与粘着斑激酶和活性细胞外信号调节激酶形成复合物。我们的研究结果提供了第一个证据的作用，促上皮素在刺激膀胱癌细胞的迁移和侵袭，并支持这一假设，即这种生长因子可能发挥关键作用，在建立侵袭性表型。
The growth factor proepithelin (also known as progranulin, acrogranin, PC-derived growth factor, or granulin-epithelin precursor) is a secreted glycoprotein that functions as an important regulator of cell growth, migration, and transformation. Proepithelin is overexpressed in a great variety of cancer cell lines and clinical specimens of breast, ovarian, and renal cancer as well as glioblastomas. In this study, we have investigated the effects of proepithelin on bladder cancer cells using human recombinant proepithelin purified to homogeneity from 293-EBNA cells. Although proepithelin did not appreciably affect cell growth, it did promote migration of 5637 bladder cancer cells and stimulate in vitro wound closure and invasion. These effects required the activation of the mitogen-activated protein kinase pathway and paxillin, which upon proepithelin stimulation formed a complex with focal adhesion kinase and active extracellular signal-regulated kinase. Our results provide the first evidence for a role of proepithelin in stimulating migration and invasion of bladder cancer cells, and support the hypothesis that this growth factor may play a critical role in the establishment of the invasive phenotype.