title: BCL6 induces EMT by promoting the ZEB1-mediated transcription repression of E-cadherin in breast cancer cells.
abstract: 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.
authors.affiliation: 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.
authors.forename: Jin-Mei
authors.initials: JM
authors.lastname: Yu
authors.affiliation: 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.
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.affiliation: 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.
authors.forename: Fang
authors.initials: F
authors.lastname: Hua
authors.affiliation: 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.
authors.forename: Jing
authors.initials: J
authors.lastname: Xie
authors.affiliation: 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.
authors.forename: Heng
authors.initials: H
authors.lastname: Lin
authors.affiliation: 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.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Zhou
authors.affiliation: 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. Electronic address: huzhuowei@imm.ac.cn.
authors.forename: Zhuo-Wei
authors.initials: ZW
authors.lastname: Hu
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D009361:Neoplasm Invasiveness / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D051560:Proto-Oncogene Proteins c-bcl-6; D034622:RNA Interference; D034741:RNA, Small Interfering; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: C084103:BCL6 protein, human; D015820:Cadherins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D034741:RNA, Small Interfering; D014157:Transcription Factors; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1
keywords: BCL6; Breast cancer; E-cadherin; EMT; ZEB1