Kuang Xia-Ying, Jiang He-Sheng, Li Kai, Zheng Yi-Zi, Liu Yi-Rong, Qiao Feng, Li Shan, Hu Xin, Shao Zhi-Ming
Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Breast Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Cancer Lett. 2016 Jul 10;377(1):87-96. doi: 10.1016/j.canlet.2016.04.035. Epub 2016 Apr 26.
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.
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。在本研究中，我们报告STMN1在Ser25和Ser38位点的磷酸化对于维持细胞迁移能力是必需的，并且与乳腺癌患者较短的无病生存期（DFS）相关。此外，我们报告分子量为78的葡萄糖调节蛋白（GRP78）是STMN1在Ser25/Ser38磷酸化后一种新的磷酸化STMN1结合蛋白。这种磷酸化依赖性相互作用受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。我们还提出了一种基于磷酸化STMN1和GRP78的预后模型，以评估乳腺癌患者的转移风险。
