Deregulation of Bmi-1 is associated with enhanced migration, invasion and poor prognosis in salivary adenoid cystic carcinoma
Deregulation of Bmi-1 is associated with enhanced migration, invasion and poor prognosis in salivary adenoid cystic carcinoma
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Bmi-1的失调与唾液腺腺样囊性癌的迁移、侵袭增强和不良预后相关
DOI：
10.1016/j.bbagen.2014.08.005
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发表时间：
2014-12-01
影响因子：
3
通讯作者：
Wang, Anxun
中科院分区：
文献类型：
--
作者：
Chang, Boyang;Li, Su;Wang, Anxun
背景：Bmi-1参与干细胞的自我更新和多种恶性肿瘤的发生。本研究探讨Bmi-1在涎腺腺样囊性癌（SACC）发生发展中的作用。方法：首先，我们证实Bmi-1的失调是SACC的常见事件; Bmi-1的上调与SACC的临床分期、生存状态和远处转移有关，并与总生存期和无病生存期降低有关。与SACC-83细胞（较低的迁移和侵袭能力）相比，SACC-LM细胞（较高的迁移和侵袭能力）提高了Bmi-1蛋白、上皮-间质转化（EMT）相关蛋白（Snail、Slug和波形蛋白）和癌症干细胞（CSC）相关蛋白（ABCG（2）、Notch、ALDH-1、Oct-4、Nanog和Epcam）的表达。Bmi-1基因敲低后，SACC-LM细胞的迁移和侵袭能力受到抑制。结论：Bmi-1基因的下调在SACC-LM细胞中起重要作用，Bmi-1基因的下调促进SACC的迁移和侵袭能力，并参与了EMT和CSC的形成。据我们所知，这是第一个研究揭示Bmi-1失调与唾液腺腺样囊性癌的迁移、侵袭和预后不良有关。(C)2014爱思唯尔有限公司版权所有。
Background: Bmi-1 had been found to involve in self renewal of stem cells and tumorigenesis in various malignancies. In this study, we investigated the role of Bmi-1 in the development of salivary adenoid cystic carcinoma (SACC).Methods: At first, we confirmed that the deregulation of Bmi-1 was a frequent event in SACC; up-regulation of Bmi-1 was correlated with clinical stages, vital status and distant metastasis and associated with reduced overall survival and disease free survival. SACC-LM cells, higher migration and invasion abilities, elevated the expression of Bmi-1 protein, epithelial-mesenchymal transition (EMT) related proteins (Snail, Slug and Vimentin) and cancer stem cells (CSCs) related proteins (ABCG(2), Notch, ALDH-1, Oct-4, Nanog and Epcam) compared to the SACC-83 cells (lower migration and invasion abilities). The migration and invasion abilities were inhibited in SACC-LM cells upon Bmi-1 knockdown. Meanwhile, Bmi-1 knockdown resulted in simultaneous loss of stem cell markers and EMT markers in SACC-LM cells.Conclusion: Our studies confirm that Bmi-1 deregulation plays an important role in the development of SACC and contributes to the migration and the invasion abilities of SACC, which is involved in EMT and CSCs.General significance: To our knowledge, this is the first study revealing that Bmi-1 deregulation is associated with enhanced migration, invasion and poor prognosis in salivary adenoid cystic carcinoma. (C) 2014 Elsevier B.V. All rights reserved.