BCL6 induces EMT by promoting the ZEB1-mediated transcription repression of E-cadherin in breast cancer cells

被引：99

作者：

Yu, Jin-Mei

Sun, Wei

Hua, Fang

Xie, Jing

Lin, Heng

Zhou, Dan-Dan

Hu, Zhuo-Wei ^{[1
]}

机构：

[1] Chinese Acad Med Sci, Inst Mat Med, State Key Lab Nat Prod Struct & Funct, Mol Immunol & Pharmacol Grp, Beijing 100050, Peoples R China

来源：

CANCER LETTERS | 2015年 / 365卷 / 02期

基金：

中国国家自然科学基金;

关键词：

Breast cancer; BCL6; EMT; E-cadherin; ZEB1; EPITHELIAL-MESENCHYMAL TRANSITION; REGULATES E-CADHERIN; IN-VITRO; STEM-CELLS; INVASION; EXPRESSION; ZEB1; MIGRATION; TUMOR; VIVO;

D O I：

10.1016/j.canlet.2015.05.029

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

B-cell CLL/Iymphoma 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. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

引用

页码：190 / 200

页数：11

共 49 条

[1] Mechanism of SMRT corepressor recruitment by the BCL6 BTB domain [J].

Ahmad, KF ;

Melnick, A ;

Lax, S ;

Bouchard, D ;

Liu, J ;

Kiang, CL ;

Mayer, S ;

Takahashi, S ;

Licht, JD ;

Privé, GG .

MOLECULAR CELL, 2003, 12 (06) :1551-1564

[2] EMT in breast cancer stem cell generation [J].

Ansieau, Stephane .

CANCER LETTERS, 2013, 338 (01) :63-68

[3] Honokiol inhibits epithelial-mesenchymal transition in breast cancer cells by targeting signal transducer and activator of transcription 3/Zeb1/E-cadherin axis [J].

Autanski, Dirniter B. ;

Nagalingam, Arumugam ;

Bonner, Michael Y. ;

Arbiser, Jack L. ;

Saxena, Neeraj K. ;

Sharma, Dipali .

MOLECULAR ONCOLOGY, 2014, 8 (03) :565-580

[4] The human BCL6 transgene promotes the development of lymphomas in the mouse [J].

Baron, BW ;

Anastasi, J ;

Montag, A ;

Huo, DZ ;

Baron, RM ;

Karrison, T ;

Thirman, MJ ;

Subudhi, SK ;

Chin, RK ;

Felsher, DW ;

Fu, YX ;

McKeithan, TW ;

Baron, JM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (39) :14198-14203

[5] Protein expression of B-cell lymphoma gene 6 (BCL-6) in invasive breast cancer is associated with cyclin D1 and hypoxia-inducible factor-1α (HIF-1α) [J].

Bos, R ;

van Diest, PJ ;

van der Groep, P ;

Greijer, AE ;

Hermsen, MA ;

Heijnen, I ;

Meijer, GA ;

Baak, JPA ;

Pinedo, HM ;

van der Wall, E ;

Shvarts, A .

ONCOGENE, 2003, 22 (55) :8948-8951

[6] A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelial-mesenchymal transition [J].

Bracken, Cameron P. ;

Gregory, Philip A. ;

Kolesnikoff, Natasha ;

Bert, Andrew G. ;

Wang, Jun ;

Shannon, M. Frances ;

Goodall, Gregory J. .

CANCER RESEARCH, 2008, 68 (19) :7846-7854

[7] Cancer cell invasion and EMT marker expression: a three-dimensional study of the human cancer-host interface [J].

Bronsert, P. ;

Enderle-Ammour, K. ;

Bader, M. ;

Timme, S. ;

Kuehs, M. ;

Csanadi, A. ;

Kayser, G. ;

Kohler, I. ;

Bausch, D. ;

Hoeppner, J. ;

Hopt, U. T. ;

Keck, T. ;

Stickeler, E. ;

Passlick, B. ;

Schilling, O. ;

Reiss, C. P. ;

Vashist, Y. ;

Brabletz, T. ;

Berger, J. ;

Lotz, J. ;

Olesch, J. ;

Werner, M. ;

Wellner, U. F. .

JOURNAL OF PATHOLOGY, 2014, 234 (03) :410-422

[8] A Small-Molecule Inhibitor of BCL6 Kills DLBCL Cells In Vitro and In Vivo [J].

Cerchietti, Leandro C. ;

Ghetu, Alexandru F. ;

Zhu, Xiao ;

Da Silva, Gustavo F. ;

Zhong, Shijun ;

Matthews, Marilyn ;

Bunting, Karen L. ;

Polo, Jose M. ;

Fares, Christophe ;

Arrowsmith, Cheryl H. ;

Yang, Shao Ning ;

Garcia, Monica ;

Coop, Andrew ;

MacKerell, Alexander D., Jr. ;

Prive, Gilbert G. ;

Melnick, Ari .

CANCER CELL, 2010, 17 (04) :400-411

[9] A peptomimetic inhibitor of BCL6 with potent antilymphoma effects in vitro and in vivo [J].

Cerchietti, Leandro C. ;

Yang, Shao Ning ;

Shaknovich, Rita ;

Hatzi, Katerina ;

Polo, Jose M. ;

Chadburn, Amy ;

Dowdy, Steven F. ;

Melnick, Ari .

BLOOD, 2009, 113 (15) :3397-3405

[10] Demethylase activity is directed by histone acetylation [J].

Cervoni, N ;

Szyf, M .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (44) :40778-40787

← 1 2 3 4 5 →