Embigin, regulated by HOXC8, plays a suppressive role in breast tumorigenesis.
Embigin, regulated by HOXC8, plays a suppressive role in breast tumorigenesis.
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Embigin 受 HOXC8 调控，在乳腺肿瘤发生中发挥抑制作用
DOI：
10.18632/oncotarget.4360
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发表时间：
2015-09-15
期刊：
影响因子：
--
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Chao F;Zhang J;Zhang Y;Liu H;Yang C;Wang J;Guo Y;Wen X;Zhang K;Huang B;Liu D;Li Y
跨膜糖蛋白embigin（EMB）属于免疫球蛋白超家族（IgSF），许多IgSF成员已被鉴定为癌症进展的生物标志物。在这项研究中，我们表明，embigin是转录调控同源框C8（HOXC 8）在乳腺癌细胞和embigin表达抑制乳腺肿瘤的发生。借助Western blot、荧光素酶报告基因分析和染色质免疫沉淀，我们发现HOXC 8与EMB启动子的-2303至-2315核苷酸区域结合，并作为转录抑制剂抑制embigin的表达。embigin的耗尽导致乳腺癌细胞的增殖、锚定非依赖性生长和迁移的增加，并且通过HOXC 8敲低介导的对乳腺肿瘤发生的抑制作用可以在很大程度上通过耗尽乳腺癌细胞中的embigin表达来挽救，这表明HOXC 8至少部分地通过调节embigin表达来调节乳腺肿瘤发生。此外，我们发现，embigin的损失促进增殖，锚定独立的生长，和正常乳腺上皮MCF 10A细胞的迁移能力。临床上可获得的人乳腺肿瘤微阵列基因表达数据库的分析显示，低embigin水平与乳腺肿瘤患者的短生存期相关，特别是基底样肿瘤患者，并且embigin表达特别在基底样ER-/HER 2-肿瘤患者中低。总之，我们的研究表明，低/损失的embigin在乳腺肿瘤的进展中起着重要的作用。
The transmembrane glycoprotein embigin (EMB) belongs to the immunoglobulin superfamily (IgSF) and a number of IgSF members have been identified as biomarkers for cancer progression. In this study, we show that embigin is transcriptionally regulated by Homeobox C8 (HOXC8) in breast cancer cells and embigin expression suppresses breast tumorigenesis. With aid of Western blot, luciferase reporter gene assay and chromatin immunoprecipitation, we reveal that HOXC8 binds to the EMB promoter at the region of nucleotides −2303 to −2315 and acts as a transcription inhibitor to suppress embigin expression. Depletion of embigin leads to increase in proliferation, anchorage-independent growth and migration of breast cancer cells, and the inhibitory effects mediated by HOXC8 knockdown on breast tumorigenesis can be largely rescued by depletion of embigin expression in breast cancer cells, suggesting that HOXC8 regulates breast tumorigenesis, at least partly, through regulating embigin expression. Moreover, we show that loss of embigin promotes proliferation, anchorage-independent growth, and migration ability of normal mammary epithelial MCF10A cells. The analyses of publically available human breast tumor microarray gene expression database show that low embigin levels correlate with short survival of breast tumor patients, particularly with basal-like tumor patients, and embigin expression is low specifically in patients with basal-like, ER-/HER2- tumors. Taken together, our study demonstrates that low/loss of embigin plays an important role in the progression of breast tumors.