Antagonistic regulation of EMT by TIF1γ and Smad4 in mammary epithelial cells

被引：58
作者：
Hesling, Cedric [1 ,2 ,3 ]
Fattet, Laurent [1 ,2 ,4 ]
Teyre, Guillaume [3 ]
Jury, Delphine [3 ]
Gonzalo, Philippe [1 ,2 ,4 ]
Lopez, Jonathan [1 ,2 ,4 ]
Vanbelle, Christophe [4 ]
Morel, Anne-Pierre [1 ,2 ,3 ]
Gillet, Germain [1 ,2 ,3 ,4 ]
Mikaelian, Ivan [1 ,2 ,3 ,4 ]
Rimokh, Ruth [1 ,2 ,3 ,4 ]
机构：
[1] Ctr Rech Cancerol Lyon, INSERM, U1052, Lyon, France
[2] CNRS, UMR5286, Lyon, France
[3] Ctr Leon Berard, F-69373 Lyon, France
[4] Univ Lyon 1, F-69365 Lyon, France
来源：
EMBO REPORTS | 2011年 / 12卷 / 07期
关键词：
TIF1; gamma; EMT; TGF-beta; Smad; breast; BREAST-CANCER CELLS; TGF-BETA; MESENCHYMAL TRANSITION; METASTASIS; BRANCHES; PATHWAY; GROWTH;
D O I：
10.1038/embor.2011.78
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
TGF-beta is a potent inducer of epithelial-to-mesenchymal transition (EMT), a process involved in tumour invasion. TIF1 gamma participates in TGF-beta signalling. To understand the role of TIF1 gamma in TGF-beta signalling and its requirement for EMT, we analysed the TGF-beta 1 response of human mammary epithelial cell lines. A strong EMT increase was observed in TIF1 gamma-silenced cells after TGF-beta 1 treatment, whereas Smad4 inactivation completely blocked this process. Accordingly, the functions of several TIF1 gamma target genes can be linked to EMT, as shown by microarray analysis. As a negative regulator of Smad4, TIF1 gamma could be crucial for the regulation of TGF-beta signalling. Furthermore, TIF1 gamma binds to and represses the plasminogen activator inhibitor 1 promoter, demonstrating a direct role of TIF1 gamma in TGF-beta-dependent gene expression. This study shows the molecular relationship between TIF1 gamma and Smad4 in TGF-beta signalling and EMT.
引用
收藏
页码：665 / 672
页数：8
相关论文
共 23 条
[1]   Induction of EMT by twist proteins as a collateral effect of tumor-promoting inactivation of premature senescence [J].
Ansieau, Stephane ;
Bastid, Jeremy ;
Doreau, Agnes ;
Morel, Anne-Pierre ;
Bouchet, Benjamin P. ;
Thomas, Clemence ;
Fauvet, Frederique ;
Puisieux, Isabelle ;
Doglioni, Claudio ;
Piccinin, Sara ;
Maestro, Roberta ;
Voeltzel, Thibault ;
Selmi, Abdelkader ;
Valsesia-Wittmann, Sandrine ;
de Fromentel, Claude Caron ;
Puisieux, Alain .
CANCER CELL, 2008, 14 (01) :79-89
[2]   TIF1γ Controls Erythroid Cell Fate by Regulating Transcription Elongation [J].
Bai, Xiaoying ;
Kim, Jonghwan ;
Yang, Zhongan ;
Jurynec, Michael J. ;
Akie, Thomas E. ;
Lee, Joseph ;
LeBlanc, Jocelyn ;
Sessa, Anna ;
Jiang, Hong ;
DiBiase, Anthony ;
Zhou, Yi ;
Grunwald, David J. ;
Lin, Shuo ;
Cantor, Alan B. ;
Orkin, Stuart H. ;
Zon, Leonard I. .
CELL, 2010, 142 (01) :133-143
[3]   The tumor suppressor Smad4 is required for transforming growth factor β-induced epithelial to mesenchymal transition and bone metastasis of breast cancer cells [J].
Deckers, M ;
van Dinther, M ;
Buijs, J ;
Que, N ;
Löwik, C ;
van der Pluijm, G ;
ten Dijke, P .
CANCER RESEARCH, 2006, 66 (04) :2202-2209
[4]   iNKT cell development is orchestrated by different branches of TGF-β signaling [J].
Doisne, Jean-Marc ;
Bartholin, Laurent ;
Yan, Kai-Ping ;
Garcia, Celine N. ;
Duarte, Nadia ;
Le Luduec, Jean-Benoit ;
Vincent, David ;
Cyprian, Farhan ;
Horvat, Branka ;
Martel, Sylvie ;
Rimokh, Ruth ;
Losson, Regine ;
Benlagha, Kamel ;
Marie, Julien C. .
JOURNAL OF EXPERIMENTAL MEDICINE, 2009, 206 (06) :1365-1378
[5]   Germ-layer specification and control of cell growth by ectodermin, a Smad4 ubiquitin ligase [J].
Dupont, S ;
Zacchigna, L ;
Cordenonsi, M ;
Soligo, S ;
Adorno, M ;
Rugge, M ;
Piccolo, S .
CELL, 2005, 121 (01) :87-99
[6]   FAM/USP9x, a Deubiquitinating Enzyme Essential for TGFβ Signaling, Controls Smad4 Monoubiquitination [J].
Dupont, Sirio ;
Mamidi, Anant ;
Cordenonsi, Michelangelo ;
Montagner, Marco ;
Zacchigna, Luca ;
Adorno, Maddalena ;
Martello, Graziano ;
Stinchfield, Michael J. ;
Soligo, Sandra ;
Morsut, Leonardo ;
Inui, Masafumi ;
Moro, Stefano ;
Modena, Nicola ;
Argenton, Francesco ;
Newfeld, Stuart J. ;
Piccolo, Stefano .
CELL, 2009, 136 (01) :123-135
[7]   Human breast cancer cells generated by oncogenic transformation of primary mammary epithelial cells [J].
Elenbaas, B ;
Spirio, L ;
Koerner, F ;
Fleming, MD ;
Zimonjic, DB ;
Donaher, JL ;
Popescu, NC ;
Hahn, WC ;
Weinberg, RA .
GENES & DEVELOPMENT, 2001, 15 (01) :50-65
[8]   Epithelial-to-mesenchymal transition is important to metastasis, but questions remain [J].
Garber, Ken .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2008, 100 (04) :232-+
[9]   Hematopoiesis controlled by distinct TIF1γ and Smad4 branches of the TGFβ pathway [J].
He, Wei ;
Dorn, David C. ;
Erdjument-Bromage, Hediye ;
Tempst, Paul ;
Moore, Malcolm A. S. ;
Massagué, Joan .
CELL, 2006, 125 (05) :929-941
[10]   Mechanism of TGF-β signaling to growth arrest, apoptosis, and epithelial-mesenchymal transition [J].
Heldin, Carl-Henrik ;
Landström, Marene ;
Moustakas, Aristidis .
CURRENT OPINION IN CELL BIOLOGY, 2009, 21 (02) :166-176
123