Center for Molecular Medicine, Xiangya Hospital, Central South University, 87 Xiangya Road, 410008, Changsha, Hunan, China.
Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.
Biochem Biophys Res Commun. 2019 May 21;513(1):28-34. doi: 10.1016/j.bbrc.2019.03.167. Epub 2019 Mar 29.
Dysfunction of Girdin plays a crucial role in the development of a variety of tumors. Phosphorylated regulation of Girdin has been studied extensively. However, how Girdin is dephosphorylated remains unclear. In this study, we report a mechanism of Girdin dephosphorylation and the importance of this mechanism in the migration of breast cancer cells. We show that the protein phosphatase 2A (PP2A) complex can bind to Girdin via the modulating B subunit. Overexpression or knockdown of PP2A inhibits or increases the phosphorylation of Girdin at serine 1416, respectively. PP2Ac-induced Girdin dephosphorylation is involved in the inhibition of breast cancer cell migration. Furthermore, in human breast cancer samples, PP2Ac expression is negatively correlated with the phosphorylation of Girdin, and low expression of PP2Ac is correlated with tumor stage, grade and lymph node metastasis of breast cancer. These data indicate that PP2A regulates Girdin dephosphorylation and highlight the critical role of this pathway in breast cancer metastasis.
Girdin 功能障碍在多种肿瘤的发生发展中起着关键作用。Girdin 的磷酸化调控已经得到了广泛的研究。然而，Girdin 是如何去磷酸化的仍不清楚。在本研究中，我们报告了 Girdin 去磷酸化的机制及其在乳腺癌细胞迁移中的重要性。我们发现蛋白磷酸酶 2A（PP2A）复合物可以通过调节亚基与 Girdin 结合。PP2A 的过表达或敲低分别抑制或增加 Girdin 丝氨酸 1416 位点的磷酸化。PP2Ac 诱导的 Girdin 去磷酸化参与了乳腺癌细胞迁移的抑制。此外，在人乳腺癌样本中，PP2Ac 的表达与 Girdin 的磷酸化呈负相关，而 PP2Ac 的低表达与乳腺癌的肿瘤分期、分级和淋巴结转移相关。这些数据表明 PP2A 调节 Girdin 的去磷酸化，并强调了该途径在乳腺癌转移中的关键作用。
