Molecular Immunology and Pharmacology Group, The State Key Laboratory of Natural Product Structure and Function, The Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Xian Nong Tan Street, Beijing 100050, China.
Molecular Immunology and Pharmacology Group, The State Key Laboratory of Natural Product Structure and Function, The Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Xian Nong Tan Street, Beijing 100050, China.
Cancer Lett. 2015 Sep 1;365(2):190-200. doi: 10.1016/j.canlet.2015.05.029. Epub 2015 Jun 3.
B-cell CLL/lymphoma 6 (BCL6), a transcriptional repressor, is involved in the development and progression of breast cancers with uncertain mechanism. The purpose of this study is to investigate the potential effect and mechanism of BCL6 in the regulation of epithelial-mesenchymal transition (EMT), a critical cellular process for controlling the development and progression of breast cancers. We found that BCL6 promoted invasion, migration and growth by stimulating EMT in breast cancer cells. BCL6 induced EMT by enhancing the expression of transcriptional repressor ZEB1 which bound to the E-cadherin promoter and repressing the E-cadherin transcription. Deletion of ZEB1 protected against the pro-EMT roles of BCL6 by restoring the expression of E-cadherin in these cells. Moreover, inhibition of BCL6 with BCL6 inhibitor 79-6 suppressed these functions of BCL6 in breast cancer cells. These findings indicate that BCL6 promotes EMT via enhancing the ZEB1-mediated transcriptional repression of E-cadherin in breast cancer cells. Targeting BCL6 has therapeutic potential against the development and progression of breast cancer.
B 细胞慢性淋巴细胞白血病/淋巴瘤 6（BCL6）是一种转录抑制剂，参与了乳腺癌的发生和发展，但具体机制尚不清楚。本研究旨在探讨 BCL6 在调控上皮间质转化（EMT）中的潜在作用和机制，EMT 是控制乳腺癌发生和发展的关键细胞过程。我们发现，BCL6 通过刺激乳腺癌细胞的 EMT 促进了侵袭、迁移和生长。BCL6 通过增强转录抑制剂 ZEB1 的表达来诱导 EMT，ZEB1 与 E-钙黏蛋白启动子结合并抑制 E-钙黏蛋白转录。ZEB1 的缺失通过恢复这些细胞中 E-钙黏蛋白的表达，阻止了 BCL6 的促 EMT 作用。此外，BCL6 抑制剂 79-6 抑制 BCL6 可抑制 BCL6 在乳腺癌细胞中的这些功能。这些发现表明，BCL6 通过增强 ZEB1 介导的 E-钙黏蛋白转录抑制来促进乳腺癌细胞中的 EMT。靶向 BCL6 具有针对乳腺癌发生和发展的治疗潜力。
