SOX2 Promotes Brain Metastasis of Breast Cancer by Upregulating the Expression of FSCN1 and HBEGF
SOX2 Promotes Brain Metastasis of Breast Cancer by Upregulating the Expression of FSCN1 and HBEGF
复制标题
SOX2通过上调FSCN1和HBEGF的表达促进乳腺癌脑转移
DOI：
10.1016/j.omto.2020.03.001
复制
发表时间：
2020-06-26
影响因子：
5.7
通讯作者：
Xie, Xiaoming
中科院分区：
文献类型：
--
作者：
Xiao, Weikai;Zheng, Shaoquan;Xie, Xiaoming
乳腺癌脑转移（BCBM）的预后极差，由于其抵抗常规治疗。阐明BCBM的分子机制有助于开发新的治疗靶点。在这项研究中，我们从原发性乳腺癌或BCBM中分离RNA样本，然后进行mRNA分析。我们确定SOX 2与BCBM的发生相关，并可能是BCBM的预测因子。高水平的SOX 2与患者无BCBM生存率降低显著相关。在乳腺癌细胞中过表达SOX 2增强了癌细胞与脑微血管内皮细胞的粘附、跨内皮迁移和体外血脑屏障（BBB）迁移，而沉默SOX 2抑制了这些事件。SOX 2可通过上调FSCN 1和HBEGF增加癌细胞迁移和BBB通透性，从而促进乳腺癌细胞的BBB迁移。此外，高水平的FSCN 1和HBEGF与乳腺癌患者无BCBM生存率的降低显著相关。进一步的研究表明，SOX 2通过激活AKT和13-catenin信号通路介导HBEGF和FSCN 1的表达。此外，体内实验表明，SOX 2促进BCBM的发展。这项研究表明，SOX 2通过上调FSCN 1和HBEGF的表达来促进BCBM。
The prognosis of breast cancer brain metastasis (BCBM) is extremely poor due to its resistance to conventional therapy. Elucidation of the molecular mechanisms of BCBM could contribute to the development of new therapeutic targets. In this study, we isolated RNA samples from primary breast cancer or BCBM, and then performed mRNA profiling. We determined that SOX2 is associated with the occurrence of BCBM and could be a predictor of BCBM. High levels of SOX2 were significantly associated with decreasing BCBM-free survival in patients. Overexpression of SOX2 in breast cancer cells enhanced cancer cell adhesion to brain microvascular endothelial cells, transendothelial migration, and in vitro blood-brain barrier (BBB) migration, whereas silencing SOX2 inhibited these events. SOX2 can increase cancer cell migration and BBB permeability by upregulating FSCN1 and HBEGF, thereby promoting BBB migration of breast cancer cells. Moreover, high levels of FSCN1 and HBEGF were significantly associated with reducing BCBM-free survival in breast cancer patients. Further study indicated that SOX2 mediates the expression of HBEGF and FSCN1 by activating AKT and 13-catenin signaling pathways. Additionally, in vivo experiments showed that SOX2 promotes the development of BCBM. This study demonstrated that SOX2 promotes BCBM by upregulating the expression of FSCN1 and HBEGF.