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SOX2 Promotes Brain Metastasis of Breast Cancer by Upregulating the Expression of FSCN1 and HBEGF.
Molecular Therapy: Oncology ( IF 5.3 ) Pub Date : 2020-03-13 , DOI: 10.1016/j.omto.2020.03.001
Weikai Xiao 1, 2 , Shaoquan Zheng 1 , Xinhua Xie 1 , Xing Li 1 , Lijuan Zhang 1 , Anli Yang 1 , Jian Wang 1 , Hailin Tang 1 , Xiaoming Xie 1
Affiliation  

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 β-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.



中文翻译:

SOX2通过上调FSCN1和HBEGF的表达促进乳腺癌的脑转移。

乳腺癌脑转移(BCBM)的预后由于对常规疗法的抵抗性而非常差。阐明BCBM的分子机制可能有助于开发新的治疗靶标。在这项研究中,我们从原发性乳腺癌或BCBM中分离了RNA样品,然后进行了mRNA分析。我们确定SOX2与BCBM的发生有关,并且可能是BCBM的预测因子。高水平的SOX2与患者无BCBM存活率下降显着相关。乳腺癌细胞中SOX2的过表达增强了癌细胞对脑微血管内皮细胞的粘附力,跨内皮迁移和体外作用血脑屏障(BBB)迁移,而使SOX2沉默则抑制了这些事件。SOX2可以通过上调FSCN1和HBEGF来增加癌细胞的迁移和BBB的通透性,从而促进乳腺癌细胞的BBB迁移。此外,高水平的FSCN1和HBEGF与降低乳腺癌患者的无BCBM生存率显着相关。进一步的研究表明,SOX2通过激活AKT和β-catenin信号通路来介导HBEGF和FSCN1的表达。另外,体内实验表明SOX2促进BCBM的发展。这项研究表明SOX2通过上调FSCN1和HBEGF的表达来促进BCBM。

更新日期:2020-03-13
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