The ZEB/miR-200 feedback loop-a motor of cellular plasticity in development and cancer?

被引:655
作者
Brabletz, Simone [1 ]
Brabletz, Thomas [1 ,2 ]
机构
[1] Univ Freiburg, Dept Visceral Surg, D-79106 Freiburg, Germany
[2] Univ Freiburg, Comprehens Canc Ctr Freiburg, D-79106 Freiburg, Germany
关键词
ZEB1; miR-200; EMT; stemness; cancer; metastasis; EPITHELIAL-MESENCHYMAL TRANSITION; GROWTH-FACTOR RECEPTOR; TRANSCRIPTIONAL REPRESSORS ZEB1; SMAD-INTERACTING PROTEIN-1; GENE-EXPRESSION SIGNATURE; REGULATES E-CADHERIN; BREAST-CANCER; MIR-200; FAMILY; STEM-CELLS; MICRORNA EXPRESSION;
D O I
10.1038/embor.2010.117
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
Epithelial-to-mesenchymal transition (EMT) is a fundamental process in development and disease. Zinc-finger enhancer binding (ZEB) transcription factors (ZEB1 and ZEB2) are crucial EMT activators, whereas members of the miR-200 family induce epithelial differentiation. They are reciprocally linked in a feedback loop, each strictly controlling the expression of the other. Now data show that EMT not only confers cellular motility, but also induces stem-cell properties and prevents apoptosis and senescence. Thus the balanced expression of ZEB factors and miR-200 controls all these processes. We therefore propose that the ZEB/miR-200 feedback loop is the molecular motor of cellular plasticity in development and disease, and in particular is a driving force for cancer progression towards metastasis by controlling the state of cancer stem cells.
引用
收藏
页码:670 / 677
页数:8
相关论文
共 84 条
[61]   Tumor response to combination celecoxib and erlotinib therapy in non-small cell lung cancer is associated with a low baseline matrix metalloproteinase-9 and a decline in serum-soluble E-cadherin [J].
Reckamp, Karen L. ;
Gardner, Brian K. ;
Figlin, Robert A. ;
Elashoff, David ;
Krysan, Kostyamyn ;
Dohadwala, Mariam ;
Mao, Jenny ;
Sharma, Sherven ;
Inge, Landon ;
Rajasekaran, Ayyappan ;
Dubinett, Steven M. .
JOURNAL OF THORACIC ONCOLOGY, 2008, 3 (02) :117-124
[62]   Differential expression of the epithelial-mesenchymal transition regulators snail, SIP1, and twist in gastric cancer [J].
Rosivatz, E ;
Becker, I ;
Specht, K ;
Fricke, E ;
Luber, B ;
Busch, R ;
Höfler, H ;
Becker, KF .
AMERICAN JOURNAL OF PATHOLOGY, 2002, 161 (05) :1881-1891
[63]   ZEB1 represses E-cadherin and induces an EMT by recruiting the SWI/SNF chromatin-remodeling protein BRG1 [J].
Sanchez-Tillo, E. ;
Lazaro, A. ;
Torrent, R. ;
Cuatrecasas, M. ;
Vaquero, E. C. ;
Castells, A. ;
Engel, P. ;
Postigo, A. .
ONCOGENE, 2010, 29 (24) :3490-3500
[64]   SIP1 protein protects cells from DNA damage-induced apoptosis and has independent prognostic value in bladder cancer [J].
Sayan, A. Emre ;
Griffiths, Thomas R. ;
Pal, Raj ;
Browne, Gareth J. ;
Ruddick, Andrew ;
Yagci, Tamer ;
Edwards, Richard ;
Mayer, Nick J. ;
Qazi, Hasan ;
Goyal, Sandeep ;
Fernandez, Serena ;
Straatman, Kees ;
Jones, George D. D. ;
Bowman, Karen J. ;
Colquhoun, Alexandra ;
Mellon, J. Kilian ;
Kriajevska, Marina ;
Tulchinsky, Eugene .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (35) :14884-14889
[65]   mir-200c Regulates Induction of Apoptosis through CD95 by Targeting FAP-1 [J].
Schickel, Robert ;
Park, Sun-Mi ;
Murmann, Andrea E. ;
Peter, Marcus E. .
MOLECULAR CELL, 2010, 38 (06) :908-915
[66]   Development and characterization of gemcitabine-resistant pancreatic tumor cells [J].
Shah, Ami N. ;
Summy, Justin M. ;
Zhang, Jing ;
Park, Serk In ;
Parikh, Nila U. ;
Gallick, Gary E. .
ANNALS OF SURGICAL ONCOLOGY, 2007, 14 (12) :3629-3637
[67]   Downregulation of miRNA-200c Links Breast Cancer Stem Cells with Normal Stem Cells [J].
Shimono, Yohei ;
Zabala, Maider ;
Cho, Robert W. ;
Lobo, Neethan ;
Dalerba, Piero ;
Qian, Dalong ;
Diehn, Maximilian ;
Liu, Huiping ;
Panula, Sarita P. ;
Chiao, Eric ;
Dirbas, Frederick M. ;
Somlo, George ;
Pera, Renee A. Reijo ;
Lao, Kaiqin ;
Clarke, Michael F. .
CELL, 2009, 138 (03) :592-603
[68]   A Gene Expression Signature Associated with "K-Ras Addiction" Reveals Regulators of EMT and Tumor Cell Survival [J].
Singh, Anurag ;
Greninger, Patricia ;
Rhodes, Daniel ;
Koopman, Louise ;
Violette, Sheila ;
Bardeesy, Nabeel ;
Settleman, Jeff .
CANCER CELL, 2009, 15 (06) :489-500
[69]   ZEB1 expression in type I vs type II endometrial cancers:: a marker of aggressive disease [J].
Singh, Meenakshi ;
Spoelstra, Nicole S. ;
Jean, Annie ;
Howe, Erin ;
Torkko, Kathleen C. ;
Clark, Hilda R. ;
Darling, Douglas S. ;
Shroyer, Kenneth R. ;
Horwitz, Kathryn B. ;
Broaddus, Russell R. ;
Richer, Jennifer K. .
MODERN PATHOLOGY, 2008, 21 (07) :912-923
[70]   The miR200 Family of MicroRNAs Regulates WAVE3-dependent Cancer Cell Invasion [J].
Sossey-Alaoui, Khalid ;
Bialkowska, Katarzyna ;
Plow, Edward F. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (48) :33019-33029