SMC1 promotes epithelial-mesenchymal transition in triple-negative breast cancer through upregulating Brachyury
SMC1 promotes epithelial-mesenchymal transition in triple-negative breast cancer through upregulating Brachyury
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SMC1通过上调Brachyury促进三阴性乳腺癌的上皮-间质转化
DOI：
10.3892/or.2016.4564
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发表时间：
2016-04-01
期刊：
影响因子：
4.2
通讯作者：
Wang, Yajie
中科院分区：
文献类型：
--
作者：
Li, Kaichun;Ying, Mingzhen;Wang, Yajie
三阴性乳腺癌（TNBC）是乳腺癌的一种特殊亚型，其特征是雌激素受体（ER）、孕激素受体（PR）和人上皮生长因子受体2（HER2）呈阴性形式。 TNBC 约占所有乳腺癌形式的 15%，通常导致高死亡率和不良预后。 1 号染色体结构维持 (SMC1) 是凝聚蛋白复合物的一个亚基。 Brachyury 是一种由人类 T 基因编码的蛋白质，T 基因是 T 盒基因复合体中的转录因子。上皮间质转化（EMT）是体内普遍存在的过程，特别是诱导癌细胞的转移和增殖。在本研究中，我们发现SMC1在TNBC组织中的表达超过其在邻近非肿瘤组织中的表达。同样，发现 TNBC 细胞系（hs578T 和 HCC1937）中 SMC1 的表达高于 MCF10a 和 MCF7 细胞。随后，分别通过质粒和siRNA转染在hs578T和HCC1937细胞中过度表达和沉默SMC1。结果显示，SMC1的高表达往往促进EMT，同时伴随着Brachyury表达的增强。此外，通过质粒转染上调Brachyury的表达也显着提高了EMT水平，这进一步表明SMC1通过诱导Brachyury表达来增加TNBC的EMT。综上所述，这些结果有助于更好地了解TNBC的发病机制，也为TNBC的预防、诊断和治疗提供了实验依据。
Triple-negative breast cancer (TNBC) is a special subtype of breast cancer, which is characterized by the negative form of estrogen receptor (ER), progesterone receptor (PR) and human epithelial growth factor receptor 2 (HER2). TNBC accounts for similar to 15% of all breast cancer forms, and often leads to high mortality and poor prognosis. Structural maintenance of chromosome 1 (SMC1) is a subunit of the cohesion protein complex. Brachyury is a protein that is encoded by the T gene in humans, which is a transcription factor within the T-box complex of genes. Epithelial-mesenchymal transition (EMT) is a ubiquitous process in the body, and in particular, induces metastasis and the proliferation of cancer cells. In the present study, we found that SMC1 expression in TNBC tissues exceeded its expression in adjacent non-tumor tissues. Similarly, the expression of SMC1 in TNBC cell lines (hs578T and HCC1937) was found to be higher than in MCF10a and MCF7 cells. Subsequently, SMC1 was overexpressed and silenced in hs578T and HCC1937 cells through plasmid and siRNA transfection, respectively. The results showed that the high expression of SMC1 often promoted EMT, accompanied by the enhanced expression of Brachyury. Besides, upregulated expression of Brachyury through plasmid transfection also significantly improved the level of EMT, which further indicated that SMC1 increased EMT in TNBC through the induction of Brachyury expression. Taken together, these results contributed to a better understanding of the pathogenesis of TNBC, which also provided an experimental basis for the prevention, diagnosis and treatment of TNBC.