Endoglin phosphorylation by ALK2 contributes to the regulation of prostate cancer cell migration
Endoglin phosphorylation by ALK2 contributes to the regulation of prostate cancer cell migration
复制标题
DOI：
10.1093/carcin/bgp217
复制
发表时间：
2010-03-01
期刊：
影响因子：
4.7
通讯作者：
Vary, Calvin P. H.
中科院分区：
文献类型：
--
作者：
Romero, Diana;Terzic, Aleksandra;Vary, Calvin P. H.
内皮糖蛋白是一种跨膜糖蛋白，作为转化生长因子-β（TGF-β）辅助受体，在PC 3-M转移性前列腺癌细胞中下调。当恢复时，PC 3-M细胞中的内皮糖蛋白表达抑制体外细胞迁移并减弱SCID小鼠中PC 3-M细胞的致瘤性，尽管前列腺癌细胞中内皮糖蛋白调节迁移的机制尚不清楚。目前的研究表明，在前列腺癌细胞中，内皮糖蛋白在胞质结构域苏氨酸残基上被TGF-β I型受体ALK 2和ALK 5磷酸化。重要的是，在存在组成型活性ALK 2的情况下，内皮糖蛋白不抑制细胞迁移，表明内皮糖蛋白磷酸化调节PC 3-M细胞迁移。因此，我们的研究结果表明，内皮糖蛋白磷酸化是一种机制，在前列腺癌细胞相关的功能后果。这些数据首次证明TGF-β受体介导的内皮素磷酸化是一种不依赖Smad的机制，参与前列腺癌细胞迁移的调节。
Endoglin, a transmembrane glycoprotein that acts as a transforming growth factor-beta (TGF-beta) coreceptor, is downregulated in PC3-M metastatic prostate cancer cells. When restored, endoglin expression in PC3-M cells inhibits cell migration in vitro and attenuates the tumorigenicity of PC3-M cells in SCID mice, though the mechanism of endoglin regulation of migration in prostate cancer cells is not known. The current study indicates that endoglin is phosphorylated on cytosolic domain threonine residues by the TGF-beta type I receptors ALK2 and ALK5 in prostate cancer cells. Importantly, in the presence of constitutively active ALK2, endoglin did not inhibit cell migration, suggesting that endoglin phosphorylation regulated PC3-M cell migration. Therefore, our results suggest that endoglin phosphorylation is a mechanism with relevant functional consequences in prostate cancer cells. These data demonstrate for the first time that TGF-beta receptor-mediated phosphorylation of endoglin is a Smad-independent mechanism involved in the regulation of prostate cancer cell migration.