The phosphorylation-specific association of STMN1 with GRP78 promotes breast cancer metastasis
The phosphorylation-specific association of STMN1 with GRP78 promotes breast cancer metastasis
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DOI：
10.1016/j.canlet.2016.04.035
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发表时间：
2016-07-10
期刊：
影响因子：
9.7
通讯作者：
Shao, Zhi-Ming
中科院分区：
文献类型：
--
作者：
Kuang, Xia-Ying;Jiang, He-Sheng;Shao, Zhi-Ming
转移是乳腺癌患者死亡的主要原因。Stathmin1 （STMN1）是一种与癌症转移相关的磷酸化蛋白。它在响应各种细胞外信号时表现出复杂的磷酸化模式，但其信号传导机制尚不清楚。在这项研究中，我们报道STMN1在Ser25和Ser38位点的磷酸化对于维持细胞迁移能力是必要的，并且与乳腺癌中较短的无病生存期（DFS）相关。此外，我们报道葡萄糖调节蛋白分子量78 （GRP78）是STMN1 Ser25/Ser38磷酸化的一种新的磷酸化-STMN1结合蛋白。这种磷酸化依赖的相互作用由MEK激酶调节，是STMN1-GRP78复合物稳定性和stmn1介导的迁移所必需的。我们还提出了一个基于phospho-STMN1和GRP78的预后模型来评估乳腺癌患者的转移风险。2016爱思唯尔爱尔兰有限公司版权所有。
Metastasis is a major cause of death in patients with breast cancer. Stathmin1 (STMN1) is a phosphoprotein associated with cancer metastasis. It exhibits a complicated phosphorylation pattern in response to various extracellular signals, but its signaling mechanism is poorly understood. In this study, we report that phosphorylation of STMN1 at Ser25 and Ser38 is necessary to maintain cell migration capabilities and is associated with shorter disease-free survival (DFS) in breast cancer. In addition, we report that glucose-regulated protein of molecular mass 78 (GRP78) is a novel phospho-STMN1 binding protein upon STMN1 Ser25/Ser38 phosphorylation. This phosphorylation-dependent interaction is regulated by MEK kinase and is required for STMN1-GRP78 complex stability and STMN1-mediated migration. We also propose a prognostic model based on phospho-STMN1 and GRP78 to assess metastatic risk in breast cancer patients. (C) 2016 Elsevier Ireland Ltd. All rights reserved.