Mithramycin inhibits epithelial-to-mesenchymal transition and invasion by downregulating SP1 and SNAI1 in salivary adenoid cystic carcinoma
Mithramycin inhibits epithelial-to-mesenchymal transition and invasion by downregulating SP1 and SNAI1 in salivary adenoid cystic carcinoma
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DOI：
10.1177/1010428317708697
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发表时间：
2017-06-20
期刊：
影响因子：
--
通讯作者：
Yin, Lin
中科院分区：
文献类型：
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作者：
Li, Jiasu;Gao, Hongmei;Yin, Lin
米霉素对胶质瘤、转移性脑癌、恶性淋巴瘤、绒毛膜癌和乳腺癌有一定的抗癌作用。然而，其对唾液腺样囊性癌的作用尚不清楚。在这里，我们报道米霉素显著抑制人唾液腺样囊性癌细胞系上皮向间质转化和侵袭。这种活性的潜在机制进一步被证明与降低转录因子特异性蛋白1和SNAI1的表达有关。特异性蛋白1是一种在SACC-LM和SACC-83细胞中过表达的促肿瘤转录因子，其表达被米霉素抑制。此外，染色质免疫沉淀实验显示特异性蛋白1通过直接结合SNAI1启动子诱导SNAI1转录。综上所述，本研究揭示了米霉素通过下调特异性蛋白1和SNAI1表达抑制唾液腺样囊性癌细胞系上皮向间质转化和侵袭的机制，提示米霉素可能是一种有前景的治疗唾液腺样囊性癌的选择。
Mithramycin exhibits certain anticancer effects in glioma, metastatic cerebral carcinoma, malignant lymphoma, chorionic carcinoma and breast cancer. However, its effects on salivary adenoid cystic carcinoma remain unclear. Here, we report that mithramycin significantly inhibited epithelial-to-mesenchymal transition and invasion in human salivary adenoid cystic carcinoma cell lines. The underlying mechanism for this activity was further demonstrated to involve decreasing the expression of the transcription factors specificity protein 1 and SNAI1. Specificity protein 1 is a pro-tumourigenic transcription factor that is overexpressed in SACC-LM and SACC-83 cells, and its expression is inhibited by mithramycin. Moreover, chromatin immunoprecipitation assays showed that specificity protein 1 induced SNAI1 transcription through direct binding to the SNAI1 promoter. In summary, this study uncovered the mechanism through which mithramycin inhibits epithelial-to-mesenchymal transition and invasion in salivary adenoid cystic carcinoma cell lines, namely, via downregulating specificity protein 1 and SNAI1 expression, which suggests mithramycin may be a promising therapeutic option for salivary adenoid cystic carcinoma.