Epithelial-Mesenchymal Transitions in Development and Disease

Cell - Tập 139 Số 5 - Trang 871-890 - 2009
Jean Paul Thiery1,2,3, Hervé Acloque4, Ruby Yun‐Ju Huang1,5,3, M. Ángela Nieto4
1Cancer Science Institute, National University of Singapore, 28 Medical Drive, Singapore 117456, Republic of Singapore
2Experimental Therapeutics Centre, 31 Biopolis Drive, Singapore 138669, Republic of Singapore
3IMCB, A∗STAR, Proteos, 61 Biopolis Drive, Singapore 138673, Republic of Singapore
4Instituto de Neurociencias CSIC-UMH, Avenida Ramón y Cajal s/n, San Juan de Alicante 03550, Spain
5Department of Obstetrics and Gynaecology, National University Hospital, Singapore 119074, Republic of Singapore

Tóm tắt

Từ khóa


Tài liệu tham khảo

Ahmed, 2006, Molecular pathways regulating EGF-induced epithelio-mesenchymal transition in human ovarian surface epithelium, Am. J. Physiol. Cell Physiol., 290, C1532, 10.1152/ajpcell.00478.2005

Ahmed, 2007, Mechanisms of palatal epithelial seam disintegration by transforming growth factor (TGF) beta3, Dev. Biol., 309, 193, 10.1016/j.ydbio.2007.06.018

Ansieau, 2008, Induction of EMT by twist proteins as a collateral effect of tumor-promoting inactivation of premature senescence, Cancer Cell, 14, 79, 10.1016/j.ccr.2008.06.005

Arnold, 2008, Pivotal roles for eomesodermin during axis formation, epithelium-to-mesenchyme transition and endoderm specification in the mouse, Development, 135, 501, 10.1242/dev.014357

Arnoux, 2008, Erk5 controls slug expression and keratinocyte activation during wound healing, Mol. Biol. Cell, 19, 4738, 10.1091/mbc.E07-10-1078

Barr, 2008, Bypassing cellular EGF receptor dependence through epithelial-to-mesenchymal-like transitions, Clin. Exp. Metastasis, 25, 685, 10.1007/s10585-007-9121-7

Barrallo-Gimeno, 2005, The Snail genes as inducers of cell movement and survival: implications in development and cancer, Development, 132, 3151, 10.1242/dev.01907

Batlle, 2000, The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells, Nat. Cell Biol., 2, 84, 10.1038/35000034

Beltran, 2008, A natural antisense transcript regulates Zeb2/Sip1 gene expression during Snail1-induced epithelial-mesenchymal transition, Genes Dev., 22, 756, 10.1101/gad.455708

Billottet, 2008, Modulation of several waves of gene expression during FGF-1 induced epithelial-mesenchymal transition of carcinoma cells, J. Cell. Biochem., 104, 826, 10.1002/jcb.21667

Boutet, 2006, Snail activation disrupts tissue homeostasis and induces fibrosis in the adult kidney, EMBO J., 25, 5603, 10.1038/sj.emboj.7601421

Brabletz, 2001, Variable beta-catenin expression in colorectal cancers indicates tumor progression driven by the tumor environment, Proc. Natl. Acad. Sci. USA, 98, 10356, 10.1073/pnas.171610498

Brabletz, 2005, Opinion: migrating cancer stem cells - an integrated concept of malignant tumour progression, Nat. Rev. Cancer, 5, 744, 10.1038/nrc1694

Broders-Bondon, 2007, Regulation of XSnail2 expression by Rho GTPases, Dev. Dyn., 236, 2555, 10.1002/dvdy.21273

Buck, 2007, Loss of homotypic cell adhesion by epithelial-mesenchymal transition or mutation limits sensitivity to epidermal growth factor receptor inhibition, Mol. Cancer Ther., 6, 532, 10.1158/1535-7163.MCT-06-0462

Buckingham, 2003, The formation of skeletal muscle: from somite to limb, J. Anat., 202, 59, 10.1046/j.1469-7580.2003.00139.x

Burk, 2008, A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells, EMBO Rep., 9, 582, 10.1038/embor.2008.74

Cano, 2008, Non-coding RNAs take centre stage in epithelial-to-mesenchymal transition, Trends Cell Biol., 18, 357, 10.1016/j.tcb.2008.05.005

Cano, 2000, The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression, Nat. Cell Biol., 2, 76, 10.1038/35000025

Carmona-Fontaine, 2008, Contact inhibition of locomotion in vivo controls neural crest directional migration, Nature, 456, 957, 10.1038/nature07441

Carver, 2001, The mouse snail gene encodes a key regulator of the epithelial-mesenchymal transition, Mol. Cell. Biol., 21, 8184, 10.1128/MCB.21.23.8184-8188.2001

Cheng, 2007, Twist transcriptionally up-regulates AKT2 in breast cancer cells leading to increased migration, invasion, and resistance to paclitaxel, Cancer Res., 67, 1979, 10.1158/0008-5472.CAN-06-1479

Christoffersen, 2007, miR-200b mediates post-transcriptional repression of ZFHX1B, RNA, 13, 1172, 10.1261/rna.586807

Chu, 2006, Prototypical type I E-cadherin and type II cadherin-7 mediate very distinct adhesiveness through their extracellular domains, J. Biol. Chem., 281, 2901, 10.1074/jbc.M506185200

Chua, 2008, Targeted therapies in control of EMT in carcinoma and fibrosis, Drug Discov. Today, 4, 261, 10.1016/j.ddmec.2008.06.002

Ciruna, 2001, FGF signaling regulates mesoderm cell fate specification and morphogenetic movement at the primitive streak, Dev. Cell, 1, 37, 10.1016/S1534-5807(01)00017-X

Cochrane, 2009, MicroRNA-200c mitigates invasiveness and restores sensitivity to microtubule-targeting chemotherapeutic agents, Mol. Cancer Ther., 8, 1055, 10.1158/1535-7163.MCT-08-1046

Coles, 2007, A critical role for Cadherin6B in regulating avian neural crest emigration, Dev. Biol., 312, 533, 10.1016/j.ydbio.2007.09.056

Combes, 2009, Endothelial cell migration directs testis cord formation, Dev. Biol., 326, 112, 10.1016/j.ydbio.2008.10.040

Condeelis, 2003, Intravital imaging of cell movement in tumours, Nat. Rev. Cancer, 3, 921, 10.1038/nrc1231

Cornell, 2005, Notch in the pathway: the roles of Notch signaling in neural crest development, Semin. Cell Dev. Biol., 16, 663, 10.1016/j.semcdb.2005.06.009

Dale, 2006, Oscillations of the snail genes in the presomitic mesoderm coordinate segmental patterning and morphogenesis in vertebrate somitogenesis, Dev. Cell, 10, 355, 10.1016/j.devcel.2006.02.011

De Calisto, 2005, Essential role of non-canonical Wnt signalling in neural crest migration, Development, 132, 2587, 10.1242/dev.01857

del Barrio, 2002, Overexpression of Snail family members highlights their ability to promote chick neural crest formation, Development, 129, 1583, 10.1242/dev.129.7.1583

Dohadwala, 2006, Cyclooxygenase-2-dependent regulation of E-cadherin: prostaglandin E(2) induces transcriptional repressors ZEB1 and snail in non-small cell lung cancer, Cancer Res., 66, 5338, 10.1158/0008-5472.CAN-05-3635

Dudas, 2007, Palatal fusion - where do the midline cells go? A review on cleft palate, a major human birth defect, Acta Histochem., 109, 1, 10.1016/j.acthis.2006.05.009

Eastham, 2007, Epithelial-mesenchymal transition events during human embryonic stem cell differentiation, Cancer Res., 67, 11254, 10.1158/0008-5472.CAN-07-2253

Egea, 2008, Genetic ablation of FLRT3 reveals a novel morphogenetic function for the anterior visceral endoderm in suppressing mesoderm differentiation, Genes Dev., 22, 3349, 10.1101/gad.486708

Escriva, 2008, Repression of PTEN phosphatase by Snail1 transcriptional factor during gamma radiation-induced apoptosis, Mol. Cell. Biol., 28, 1528, 10.1128/MCB.02061-07

Evdokimova, 2009, Translational activation of snail1 and other developmentally regulated transcription factors by YB-1 promotes an epithelial-mesenchymal transition, Cancer Cell, 15, 402, 10.1016/j.ccr.2009.03.017

Fan, 2007, Cell contact-dependent regulation of epithelial-myofibroblast transition via the rho-rho kinase-phospho-myosin pathway, Mol. Biol. Cell, 18, 1083, 10.1091/mbc.E06-07-0602

Feldmann, 2007, Blockade of hedgehog signaling inhibits pancreatic cancer invasion and metastases: a new paradigm for combination therapy in solid cancers, Cancer Res., 67, 2187, 10.1158/0008-5472.CAN-06-3281

Fendrich, 2007, Snail and Sonic Hedgehog activation in neuroendocrine tumors of the ileum, Endocr. Relat. Cancer, 14, 865, 10.1677/ERC-07-0108

Fiaschi, 2007, Targeted expression of GLI1 in the mammary gland disrupts pregnancy-induced maturation and causes lactation failure, J. Biol. Chem., 282, 36090, 10.1074/jbc.M704280200

Finn, 2007, Dasatinib, an orally active small molecule inhibitor of both the src and abl kinases, selectively inhibits growth of basal-type/”triple-negative” breast cancer cell lines growing in vitro, Breast Cancer Res. Treat., 105, 319, 10.1007/s10549-006-9463-x

Fischer, 2007, Combined loss of Hey1 and HeyL causes congenital heart defects because of impaired epithelial to mesenchymal transition, Circ. Res., 100, 856, 10.1161/01.RES.0000260913.95642.3b

Fraga, 2004, A mouse skin multistage carcinogenesis model reflects the aberrant DNA methylation patterns of human tumors, Cancer Res., 64, 5527, 10.1158/0008-5472.CAN-03-4061

Frederick, 2007, Epithelial to mesenchymal transition predicts gefitinib resistance in cell lines of head and neck squamous cell carcinoma and non-small cell lung carcinoma, Mol. Cancer Ther., 6, 1683, 10.1158/1535-7163.MCT-07-0138

Fujita, 2003, MTA3, a Mi-2/NuRD complex subunit, regulates an invasive growth pathway in breast cancer, Cell, 113, 207, 10.1016/S0092-8674(03)00234-4

Gal, 2008, Sustained TGF beta exposure suppresses Smad and non-Smad signalling in mammary epithelial cells, leading to EMT and inhibition of growth arrest and apoptosis, Oncogene, 27, 1218, 10.1038/sj.onc.1210741

Gibbons, 2009, Contextual extracellular cues promote tumor cell EMT and metastasis by regulating miR-200 family expression, Genes Dev., 15, 2140, 10.1101/gad.1820209

Gilbert, 2006

Gotzmann, 2006, A crucial function of PDGF in TGF-beta-mediated cancer progression of hepatocytes, Oncogene, 25, 3170, 10.1038/sj.onc.1209083

Graham, 2008, Insulin-like growth factor-I-dependent up-regulation of ZEB1 drives epithelial-to-mesenchymal transition in human prostate cancer cells, Cancer Res., 68, 2479, 10.1158/0008-5472.CAN-07-2559

Gregory, 2008, The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1, Nat. Cell Biol., 10, 593, 10.1038/ncb1722

Gros, 2005, A common somitic origin for embryonic muscle progenitors and satellite cells, Nature, 435, 954, 10.1038/nature03572

Grosshans, 2000, A genetic link between morphogenesis and cell division during formation of the ventral furrow in Drosophila, Cell, 101, 523, 10.1016/S0092-8674(00)80862-4

Grotegut, 2006, Hepatocyte growth factor induces cell scattering through MAPK/Egr-1-mediated upregulation of Snail, EMBO J., 25, 3534, 10.1038/sj.emboj.7601213

Guemar, 2007, The small GTPase RhoV is an essential regulator of neural crest induction in Xenopus, Dev. Biol., 310, 113, 10.1016/j.ydbio.2007.07.031

Gumireddy, 2009, KLF17 is a negative regulator of epithelial-mesenchymal transition and metastasis ein breast cancer, Nat. Cell Biol., 11, 1297, 10.1038/ncb1974

Gupta, 2009, Identification of selective inhibitors of cancer stem cells by high-throughput screening, Cell, 138, 645, 10.1016/j.cell.2009.06.034

Haraguchi, 2008, Snail regulates cell-matrix adhesion by regulation of the expression of integrins and basement membrane paroteins, J. Biol. Chem., 283, 23514, 10.1074/jbc.M801125200

Heisenberg, 2008, Back and forth between cell fate specification and movement during vertebrate gastrulation, Curr. Opin. Genet. Dev., 18, 311, 10.1016/j.gde.2008.07.011

Herbst, 2005, TRIBUTE: a phase III trial of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small-cell lung cancer, J. Clin. Oncol., 23, 5892, 10.1200/JCO.2005.02.840

Hermann, 2007, Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer, Cell Stem Cell, 1, 313, 10.1016/j.stem.2007.06.002

Herranz, 2008, Polycomb complex 2 is required for E-cadherin repression by the Snail1 transcription factor, Mol. Cell. Biol., 28, 4772, 10.1128/MCB.00323-08

High, 2007, An essential role for Notch in neural crest during cardiovascular development and smooth muscle differentiation, J. Clin. Invest., 117, 353, 10.1172/JCI30070

Hirano, 2008, EPB41L5 functions to post-transcriptionally regulate cadherin and integrin during epithelial-mesenchymal transition, J. Cell Biol., 182, 1217, 10.1083/jcb.200712086

Huang, 2007, Thymosin beta4 triggers an epithelial-mesenchymal transition in colorectal carcinoma by upregulating integrin-linked kinase, Oncogene, 26, 2781, 10.1038/sj.onc.1210078

Huang, 2008, The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis, Nat. Cell Biol., 10, 202, 10.1038/ncb1681

Huber, 2004, NF-kappaB is essential for epithelial-mesenchymal transition and metastasis in a model of breast cancer progression, J. Clin. Invest., 114, 569, 10.1172/JCI200421358

Hurteau, 2007, Overexpression of the microRNA hsa-miR-200c leads to reduced expression of transcription factor 8 and increased expression of E-cadherin, Cancer Res., 67, 7972, 10.1158/0008-5472.CAN-07-1058

Hüsemann, 2008, Systemic spread is an early step in breast cancer, Cancer Cell, 13, 58, 10.1016/j.ccr.2007.12.003

Illman, 2006, Epilysin (MMP-28) induces TGF-beta mediated epithelial to mesenchymal transition in lung carcinoma cells, J. Cell Sci., 119, 3856, 10.1242/jcs.03157

Iwano, 2002, Evidence that fibroblasts derive from epithelium during tissue fibrosis, J. Clin. Invest., 110, 341, 10.1172/JCI0215518

Janda, 2006, Raf plus TGFbeta-dependent EMT is initiated by endocytosis and lysosomal degradation of E-cadherin, Oncogene, 25, 7117, 10.1038/sj.onc.1209701

Johansson, 2002, Development and diseases of the pancreas, Clin. Genet., 62, 14, 10.1034/j.1399-0004.2002.620102.x

Jorda, 2005, Upregulation of MMP-9 in MDCK epithelial cell line in response to expression of the Snail transcription factor, J. Cell Sci., 118, 3371, 10.1242/jcs.02465

Julien, 2007, Activation of NF-kappaB by Akt upregulates Snail expression and induces epithelium mesenchyme transition, Oncogene, 26, 7445, 10.1038/sj.onc.1210546

Jung, 2008, TMPRSS4 promotes invasion, migration and metastasis of human tumor cells by facilitating an epithelial-mesenchymal transition, Oncogene, 27, 2635, 10.1038/sj.onc.1210914

Kajita, 2004, Aberrant expression of the transcription factors snail and slug alters the response to genotoxic stress, Mol. Cell. Biol., 24, 7559, 10.1128/MCB.24.17.7559-7566.2004

Kajiyama, 2007, Chemoresistance to paclitaxel induces epithelial-mesenchymal transition and enhances metastatic potential for epithelial ovarian carcinoma cells, Int. J. Oncol., 31, 277

Karnoub, 2007, Mesenchymal stem cells within tumour stroma promote breast cancer metastasis, Nature, 449, 557, 10.1038/nature06188

Kelly, 2007, Tumor growth need not be driven by rare cancer stem cells, Science, 317, 337, 10.1126/science.1142596

Kim, 2007, Constitutively active type I insulin-like growth factor receptor causes transformation and xenograft growth of immortalized mammary epithelial cells and is accompanied by an epithelial-to-mesenchymal transition mediated by NF-kappaB and snail, Mol. Cell. Biol., 27, 3165, 10.1128/MCB.01315-06

Kim, 2006, Alveolar epithelial cell mesenchymal transition develops in vivo during pulmonary fibrosis and is regulated by the extracellular matrix, Proc. Natl. Acad. Sci. USA, 103, 13180, 10.1073/pnas.0605669103

Kitajima, 2000, MesP1 and MesP2 are essential for the development of cardiac mesoderm, Development, 127, 3215, 10.1242/dev.127.15.3215

Knutson, 2006, Immunoediting of cancers may lead to epithelial mesenchymal transition, J. Immunol., 177, 1526, 10.4049/jimmunol.177.3.1526

Kolsch, 2007, Control of Drosophila gastrulation by apical localization of adherens junctions and RhoGEF2, Science, 315, 384, 10.1126/science.1134833

Korpal, 2008, The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2, J. Biol. Chem., 283, 14910, 10.1074/jbc.C800074200

Kudo-Saito, 2009, Cancer metastasis is accelerated through immunosuppression during Snail-induced EMT of cancer cells, Cancer Cell, 15, 195, 10.1016/j.ccr.2009.01.023

Kurrey, 2009, Snail and slug mediate radioresistance and chemoresistance by antagonizing p53-mediated apoptosis and acquiring a stem-like phenotype in ovarian cancer cells, Stem Cells, 27, 2059, 10.1002/stem.154

Langer, 2008, Ajuba LIM proteins are snail/slug corepressors required for neural crest development in Xenopus, Dev. Cell, 14, 424, 10.1016/j.devcel.2008.01.005

Lee, 2007, The FERM protein Epb4.1l5 is required for organization of the neural plate and for the epithelial-mesenchymal transition at the primitive streak of the mouse embryo, Development, 134, 2007, 10.1242/dev.000885

Lee, 2008, Epithelial-mesenchymal transition in cervical cancer: correlation with tumor progression, epidermal growth factor receptor overexpression, and snail up-regulation, Clin. Cancer Res., 14, 4743, 10.1158/1078-0432.CCR-08-0234

Leong, 2007, Jagged1-mediated Notch activation induces epithelial-to-mesenchymal transition through Slug-induced repression of E-cadherin, J. Exp. Med., 204, 2935, 10.1084/jem.20071082

Lepilina, 2006, A dynamic epicardial injury response supports progenitor cell activity during zebrafish heart regeneration, Cell, 127, 607, 10.1016/j.cell.2006.08.052

Li, 2009, Twist1-mediated adriamycin-induced epithelial-mesenchymal transition relates to multidrug resistance and invasive potential in breast cancer cells, Clin. Cancer Res., 15, 2657, 10.1158/1078-0432.CCR-08-2372

Liang, 2007, PRL3 promotes cell invasion and proliferation by down-regulation of Csk leading to Src activation, J. Biol. Chem., 282, 5413, 10.1074/jbc.M608940200

Lindsley, 2008, Mesp1 coordinately regulates cardiovascular fate restriction and epithelial-mesenchymal transition in differentiating ESCs, Cell Stem Cell, 3, 55, 10.1016/j.stem.2008.04.004

Liu, 2008, Zeb1 links epithelial-mesenchymal transition and cellular senescence, Development, 135, 579, 10.1242/dev.007047

Lo, 2007, Epidermal growth factor receptor cooperates with signal transducer and activator of transcription 3 to induce epithelial-mesenchymal transition in cancer cells via up-regulation of TWIST gene expression, Cancer Res., 67, 9066, 10.1158/0008-5472.CAN-07-0575

López-Novoa, 2009, Inflammation and EMT: an alliance towards organ fibrosis and cancer progression, EMBO Molecular Medicine, 1, 303, 10.1002/emmm.200900043

Lu, 2003, Downregulation of caveolin-1 function by EGF leads to the loss of E-cadherin, increased transcriptional activity of beta-catenin, and enhanced tumor cell invasion, Cancer Cell, 4, 499, 10.1016/S1535-6108(03)00304-0

Lyons, 2008, Snail up-regulates proinflammatory mediators and inhibits differentiation in oral keratinocytes, Cancer Res., 68, 4525, 10.1158/1078-0432.CCR-07-6735

Lysy, 2007, Human skin fibroblasts: From mesodermal to hepatocyte-like differentiation, Hepatology, 46, 1574, 10.1002/hep.21839

Ma, 2007, Tumour invasion and metastasis initiated by microRNA-10b in breast cancer, Nature, 449, 682, 10.1038/nature06174

Maina, 2001, Coupling Met to specific pathways results in distinct developmental outcomes, Mol. Cell, 7, 1293, 10.1016/S1097-2765(01)00261-1

Mani, 2008, The epithelial-mesenchymal transition generates cells with properties of stem cells, Cell, 133, 704, 10.1016/j.cell.2008.03.027

Mann, 2006, Repression of prostaglandin dehydrogenase by epidermal growth factor and snail increases prostaglandin E2 and promotes cancer progression, Cancer Res., 66, 6649, 10.1158/0008-5472.CAN-06-1787

Martin, 2009, Pulsed actin-myosin network contractions drive apical constriction, Nature, 457, 495, 10.1038/nature07522

Martin-Villar, 2006, Podoplanin binds ERM proteins to activate RhoA and promote epithelial-mesenchymal transition, J. Cell Sci., 119, 4541, 10.1242/jcs.03218

Martínez-Álvarez, 2004, Snail family members and cell survival in physiological and pathological cleft palates, Dev. Biol., 265, 207, 10.1016/j.ydbio.2003.09.022

Massagué, 2008, TGFβ in cancer, Cell, 134, 215, 10.1016/j.cell.2008.07.001

McCoy, 2009, Six1 expands the mouse mammary epithelial stem/progenitor cell pool and induces mammary tumors that undergo epithelial-mesenchymal transition, J. Clin. Invest., 119, 2663, 10.1172/JCI37691

Medjkane, 2009, Myocardin-related transcription factors and SRF are required for cytoskeletal dynamics and experimental metastasis, Nat. Cell Biol., 11, 257, 10.1038/ncb1833

Mercado-Pimentel, 2007, Multiple transforming growth factor-beta isoforms and receptors function during epithelial-mesenchymal cell transformation in the embryonic heart, Cells Tissues Organs, 185, 146, 10.1159/000101315

Micalizzi, 2009, The Six1 homeoprotein induces human mammary carcinoma cells to undergo epithelial-mesenchymal transition and metastasis in mice through increasing TGF-beta signaling, J. Clin. Invest., 119, 2678, 10.1172/JCI37815

Min, 2007, The tumor suppressor activity of the lysyl oxidase propeptide reverses the invasive phenotype of Her-2/neu-driven breast cancer, Cancer Res., 67, 1105, 10.1158/0008-5472.CAN-06-3867

Mitiku, 2007, Genomic analysis of gastrulation and organogenesis in the mouse, Dev. Cell, 13, 897, 10.1016/j.devcel.2007.10.004

Monsoro-Burq, 2005, Sclerotome development and morphogenesis: when experimental embryology meets genetics, Int. J. Dev. Biol., 49, 301, 10.1387/ijdb.041953am

Moody, 2002, Conditional activation of Neu in the mammary epithelium of transgenic mice results in reversible pulmonary metastasis, Cancer Cell, 2, 451, 10.1016/S1535-6108(02)00212-X

Moody, 2005, The transcriptional repressor Snail promotes mammary tumor recurrence, Cancer Cell, 8, 197, 10.1016/j.ccr.2005.07.009

Morales, 2007, Snail genes at the crossroads of symmetric and asymmetric processes in the developing mesoderm, EMBO Rep., 8, 104, 10.1038/sj.embor.7400867

Morel, 2008, Generation of breast cancer stem cells through epithelial-mesenchymal transition, PLoS ONE, 3, e2888, 10.1371/journal.pone.0002888

Moreno-Bueno, 2008, Transcriptional regulation of cell polarity in EMT and cancer, Oncogene, 27, 6958, 10.1038/onc.2008.346

Morita, 2007, Dual roles of myocardin-related transcription factors in epithelial mesenchymal transition via slug induction and actin remodeling, J. Cell Biol., 179, 1027, 10.1083/jcb.200708174

Murray, 2006, Snail family genes are required for left-right asymmetry determination, but not neural crest formation, in mice, Proc. Natl. Acad. Sci. USA, 103, 10300, 10.1073/pnas.0602234103

Nakagawa, 1995, Neural crest cell-cell adhesion controlled by sequential and subpopulation-specific expression of novel cadherins, Development, 121, 1321, 10.1242/dev.121.5.1321

Nakajima, 2000, Mechanisms involved in valvuloseptal endocardial cushion formation in early cardiogenesis: roles of transforming growth factor (TGF)-beta and bone morphogenetic protein (BMP), Anat. Rec., 258, 119, 10.1002/(SICI)1097-0185(20000201)258:2<119::AID-AR1>3.0.CO;2-U

Nakaya, 2004, Mesenchymal-epithelial transition during somitic segmentation is regulated by differential roles of Cdc42 and Rac1, Dev. Cell, 7, 425, 10.1016/j.devcel.2004.08.003

Nakaya, 2008, RhoA and microtubule dynamics control cell-basement membrane interaction in EMT during gastrulation, Nat. Cell Biol., 10, 765, 10.1038/ncb1739

Nieto, 1994, Control of cell behavior during vertebrate development by Slug, a zinc finger gene, Science, 264, 835, 10.1126/science.7513443

Niessen, 2008, Slug is a direct Notch target required for initiation of cardiac cushion cellularization, J. Cell Biol., 182, 315, 10.1083/jcb.200710067

Nitta, 2008, Murine cirrhosis induces hepatocyte epithelial mesenchymal transition and alterations in survival signaling pathways, Hepatology, 48, 909, 10.1002/hep.22397

Oda, 1998, Dynamic behavior of the cadherin-based cell-cell adhesion system during Drosophila gastrulation, Dev. Biol., 203, 435, 10.1006/dbio.1998.9047

Oliveri, 2008, Global regulatory logic for specification of an embryonic cell lineage, Proc. Natl. Acad. Sci. USA, 105, 5955, 10.1073/pnas.0711220105

Olmeda, 2008, Snai1 and Snai2 collaborate on tumor growth and metastasis properties of mouse skin carcinoma cell lines, Oncogene, 27, 4690, 10.1038/onc.2008.118

Ozdamar, 2005, Regulation of the polarity protein Par6 by TGFbeta receptors controls epithelial cell plasticity, Science, 307, 1603, 10.1126/science.1105718

Park, 2008, The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2, Genes Dev., 22, 894, 10.1101/gad.1640608

Peinado, 2004, Snail and E47 repressors of E-cadherin induce distinct invasive and angiogenic properties in vivo, J. Cell Sci., 117, 2827, 10.1242/jcs.01145

Peinado, 2007, Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype?, Nat. Rev. Cancer, 7, 415, 10.1038/nrc2131

Peiro, 2006, Snail1 transcriptional repressor binds to its own promoter and controls its expression, Nucleic Acids Res., 34, 2077, 10.1093/nar/gkl141

Peña, 2006, The expression levels of the transcriptional regulators p300 and CtBP modulate the correlations between SNAIL, ZEB1, E-cadherin and vitamin D receptor in human colon carcinomas, Int. J. Cancer, 119, 2098, 10.1002/ijc.22083

Perez-Alcala, 2004, LSox5 regulates RhoB expression in the neural tube and promotes generation of the neural crest, Development, 131, 4455, 10.1242/dev.01329

Perl, 1998, A causal role for E-cadherin in the transition from adenoma to carcinoma, Nature, 392, 190, 10.1038/32433

Philippar, 2008, A Mena invasion isoform potentiates EGF-induced carcinoma cell invasion and metastasis, Dev. Cell, 15, 813, 10.1016/j.devcel.2008.09.003

Pollak, 2008, Insulin and insulin-like growth factor signalling in neoplasia, Nat. Rev. Cancer, 8, 915, 10.1038/nrc2536

Prall, 2007, Tumour budding in colorectal carcinoma, Histopathology, 50, 151, 10.1111/j.1365-2559.2006.02551.x

Puisieux, 2006, A twist for survival and cancer progression, Br. J. Cancer, 94, 13, 10.1038/sj.bjc.6602876

Quintana, 2008, Efficient tumour formation by single human melanoma cells, Nature, 456, 593, 10.1038/nature07567

Radisky, 2005, Rac1b and reactive oxygen species mediate MMP-3-induced EMT and genomic instability, Nature, 436, 123, 10.1038/nature03688

Rivera-Feliciano, 2006, Development of heart valves requires Gata4 expression in endothelial-derived cells, Development, 133, 3607, 10.1242/dev.02519

Ruan, 2009, The multifaceted role of periostin in tumorigenesis, Cell. Mol. Life Sci., 66, 2219, 10.1007/s00018-009-0013-7

Sahlgren, 2008, Notch signaling mediates hypoxia-induced tumor cell migration and invasion, Proc. Natl. Acad. Sci. USA, 105, 6392, 10.1073/pnas.0802047105

Saika, 2004, Transient adenoviral gene transfer of Smad7 prevents injury-induced epithelial-mesenchymal transition of lens epithelium in mice, Lab. Invest., 84, 1259, 10.1038/labinvest.3700151

Sakai, 2006, Cooperative action of Sox9, Snail2 and PKA signaling in early neural crest development, Development, 133, 1323, 10.1242/dev.02297

Sato, 2003, Targeted disruption of TGF-beta1/Smad3 signaling protects against renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction, J. Clin. Invest., 112, 1486, 10.1172/JCI200319270

Sauka-Spengler, 2008, A gene regulatory network orchestrates neural crest formation, Nat. Rev. Mol. Cell Biol., 9, 557, 10.1038/nrm2428

Shida, 2006, Sonic Hedgehog-Gli1 signaling pathway might become an effective therapeutic target in gastrointestinal neuroendocrine carcinomas, Cancer Biol. Ther., 5, 1530, 10.4161/cbt.5.11.3458

Shoval, 2007, Antagonistic roles of full-length N-cadherin and its soluble BMP cleavage product in neural crest delamination, Development, 134, 491, 10.1242/dev.02742

Shrader, 2007, Molecular correlates of gefitinib responsiveness in human bladder cancer cells, Mol. Cancer Ther., 6, 277, 10.1158/1535-7163.MCT-06-0513

Shtutman, 2006, Cell adhesion molecule L1 disrupts E-cadherin-containing adherens junctions and increases scattering and motility of MCF7 breast carcinoma cells, Cancer Res., 66, 11370, 10.1158/0008-5472.CAN-06-2106

Smolen, 2007, A Rap GTPase interactor, RADIL, mediates migration of neural crest precursors, Genes Dev., 21, 2131, 10.1101/gad.1561507

Sobrado, 2009, The class I bHLH factors E2-2A and E2-2B regulate EMT, J. Cell Sci., 122, 1014, 10.1242/jcs.028241

Spaderna, 2008, The transcriptional repressor ZEB1 promotes metastasis and loss of cell polarity in cancer, Cancer Res., 68, 537, 10.1158/0008-5472.CAN-07-5682

Stefani, 2008, Small non-coding RNAs in animal development, Nat. Rev. Mol. Cell Biol., 9, 219, 10.1038/nrm2347

Stemmer, 2008, Snail promotes Wnt target gene expression and interacts with beta-catenin, Oncogene, 27, 5075, 10.1038/onc.2008.140

Strippoli, 2008, Epithelial-to-mesenchymal transition of peritoneal mesothelial cells is regulated by an ERK/NF-κB/Snail1 pathway, Dis. Model. Mech., 1, 264, 10.1242/dmm.001321

Sullivan, 2009, Interleukin-6 induces an epithelial–mesenchymal transition phenotype in human breast cancer cells, Oncogene, 28, 2940, 10.1038/onc.2009.180

Tan, 2006, Paricalcitol attenuates renal interstitial fibrosis in obstructive nephropathy, J. Am. Soc. Nephrol., 17, 3382, 10.1681/ASN.2006050520

Taneyhill, 2007, Snail2 directly represses cadherin6B during epithelial-to-mesenchymal transitions of the neural crest, Development, 134, 1481, 10.1242/dev.02834

Tanimizu, 2007, Molecular mechanism of liver development and regeneration, Int. Rev. Cytol., 259, 1, 10.1016/S0074-7696(06)59001-1

Teddy, 2004, In vivo evidence for short- and long-range cell communication in cranial neural crest cells, Development, 131, 6141, 10.1242/dev.01534

Thiery, 2006, Complex networks orchestrate epithelial-mesenchymal transitions, Nat. Rev. Mol. Cell Biol., 7, 131, 10.1038/nrm1835

Thomson, 2005, Epithelial to mesenchymal transition is a determinant of sensitivity of non-small-cell lung carcinoma cell lines and xenografts to epidermal growth factor receptor inhibition, Cancer Res., 65, 9455, 10.1158/0008-5472.CAN-05-1058

Thuault, 2008, HMGA2 and Smads co-regulate SNAIL1 expression during induction of epithelial-to-mesenchymal transition, J. Biol. Chem., 174, 175

Timmerman, 2004, Notch promotes epithelial-mesenchymal transition during cardiac development and oncogenic transformation, Genes Dev., 18, 99, 10.1101/gad.276304

Ullmann, 2007, Epithelial-mesenchymal transition process in human embryonic stem cells cultured in feeder-free conditions, Mol. Hum. Reprod., 13, 21, 10.1093/molehr/gal091

Unno, 2009, LIV-1 enhances the aggressive phenotype through the induction of epithelial to mesenchymal transition in human pancreatic carcinoma cells, Int. J. Oncol., 35, 813

Valdes, 2002, The epithelial mesenchymal transition confers resistance to the apoptotic effects of transforming growth factor Beta in fetal rat hepatocytes, Mol. Cancer Res., 1, 68

Vallin, 1998, Xenopus cadherin-11 is expressed in different populations of migrating neural crest cells, Mech. Dev., 75, 171, 10.1016/S0925-4773(98)00099-9

Vega, 2004, Snail blocks the cell cycle and confers resistance to cell death, Genes Dev., 18, 1131, 10.1101/gad.294104

Vincent, 2009, SNAIL1-SMAD3/4 transcriptional repressor complex promotes TGF-beta mediated epithelial-mesenchymal transition, Nat. Cell Biol., 11, 943, 10.1038/ncb1905

Visvader, 2008, Cancer stem cells in solid tumours: accumulating evidence and unresolved questions, Nat. Rev. Cancer, 8, 755, 10.1038/nrc2499

Waerner, 2006, ILEI: a cytokine essential for EMT, tumor formation, and late events in metastasis in epithelial cells, Cancer Cell, 10, 227, 10.1016/j.ccr.2006.07.020

Wan, 2008, Inhibition of Aurora-A suppresses epithelial-mesenchymal transition and invasion by downregulating MAPK in nasopharyngeal carcinoma cells, Carcinogenesis, 29, 1930, 10.1093/carcin/bgn176

Wanami, 2008, Vascular endothelial growth factor-A stimulates Snail expression in breast tumor cells: implications for tumor progression, Exp. Cell Res., 314, 2448, 10.1016/j.yexcr.2008.05.004

Wang, 2007, PRL-3 down-regulates PTEN expression and signals through PI3K to promote epithelial-mesenchymal transition, Cancer Res., 67, 2922, 10.1158/0008-5472.CAN-06-3598

Wang, 2009, p53 controls cancer cell invasion by inducing the MDM2-mediated degradation of Slug, Nat. Cell Biol., 11, 694, 10.1038/ncb1875

Wang, 2007, Kruppel-like factor 8 induces epithelial to mesenchymal transition and epithelial cell invasion, Cancer Res., 67, 7184, 10.1158/0008-5472.CAN-06-4729

Wang, 2008, Downregulation of Par-3 expression and disruption of Par complex integrity by TGF-beta during the process of epithelial to mesenchymal transition in rat proximal epithelial cells, Biochim. Biophys. Acta, 1782, 51, 10.1016/j.bbadis.2007.11.002

Wang, 2009, LSD1 Is a Subunit of the NuRD Complex and Targets the Metastasis Programs in Breast Cancer, Cell, 138, 660, 10.1016/j.cell.2009.05.050

Warzecha, 2009, ESRP1 and ESRP2 are epithelial cell-type-specific regulators of FGFR2 splicing, Mol. Cell, 33, 591, 10.1016/j.molcel.2009.01.025

Warzecha, 2009, The epithelial splicing factors ESRP1 and ESRP2 positively and negatively regulate diverse types of alternative splicing events, RNA Biol., 6

Wellner, 2009, The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs, Nat. Cell Biol., 10.1038/ncb1998

Whiteman, 2008, The transcription factor snail represses Crumbs3 expression and disrupts apico-basal polarity complexes, Oncogene, 27, 3875, 10.1038/onc.2008.9

Wicki, 2006, Tumor invasion in the absence of epithelial-mesenchymal transition: podoplanin-mediated remodeling of the actin cytoskeleton, Cancer Cell, 9, 261, 10.1016/j.ccr.2006.03.010

Witta, 2006, Restoring E-cadherin expression increases sensitivity to epidermal growth factor receptor inhibitors in lung cancer cell lines, Cancer Res., 66, 944, 10.1158/0008-5472.CAN-05-1988

Wu, 2007, Ingression of primary mesenchyme cells of the sea urchin embryo: a precisely timed epithelial mesenchymal transition. Birth Defects Res, C Embryo Today, 81, 241, 10.1002/bdrc.20113

Wu, 2008, Twist is an essential regulator of the skeletogenic gene regulatory network in the sea urchin embryo, Dev. Biol., 319, 406, 10.1016/j.ydbio.2008.04.003

Wu, 2009, Stabilization of Snail by NF-κB is required for inflammation-induced cell migration and invasion, Cancer Cell, 15, 416, 10.1016/j.ccr.2009.03.016

Wu, 2009, Small C-terminal domain phosphatase enhances snail activity through dephosphorylation, J. Biol. Chem., 284, 640, 10.1074/jbc.M806916200

Wyatt, 2007, The protein tyrosine phosphatase Pez regulates TGFbeta, epithelial-mesenchymal transition, and organ development, J. Cell Biol., 178, 1223, 10.1083/jcb.200705035

Wyckoff, 2007, Direct visualization of macrophage-assisted tumor cell intravasation in mammary tumors, Cancer Res., 67, 2649, 10.1158/0008-5472.CAN-06-1823

Yamashita, 2004, Zinc transporter LIVI controls epithelial-mesenchymal transition in zebrafish gastrula organizer, Nature, 429, 298, 10.1038/nature02545

Yanez-Mo, 2003, Peritoneal dialysis and epithelial-to-mesenchymal transition of mesothelial cells, N. Engl. J. Med., 348, 403, 10.1056/NEJMoa020809

Yang, 2006, Vascular endothelial growth factor receptor-1 activation mediates epithelial to mesenchymal transition in human pancreatic carcinoma cells, Cancer Res., 66, 46, 10.1158/0008-5472.CAN-05-3086

Yang, 2006, Chronic oxaliplatin resistance induces epithelial-to-mesenchymal transition in colorectal cancer cell lines, Clin. Cancer Res., 12, 4147, 10.1158/1078-0432.CCR-06-0038

Yang, 2008, Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis, Dev. Cell, 14, 818, 10.1016/j.devcel.2008.05.009

Yang, 2006, P68 RNA helicase mediates PDGF-induced epithelial mesenchymal transition by displacing Axin from beta-catenin, Cell, 127, 139, 10.1016/j.cell.2006.08.036

Yang, 2008, Direct regulation of TWIST by HIF-1alpha promotes metastasis, Nat. Cell Biol., 10, 295, 10.1038/ncb1691

Yauch, 2005, Epithelial versus mesenchymal phenotype determines in vitro sensitivity and predicts clinical activity of erlotinib in lung cancer patients, Clin. Cancer Res., 11, 8686, 10.1158/1078-0432.CCR-05-1492

Zavadil, 2007, Transforming growth factor-beta and microRNA:mRNA regulatory networks in epithelial plasticity, Cells Tissues Organs, 185, 157, 10.1159/000101316

Zeisberg, 2003, Bone morphogenic protein-7 inhibits progression of chronic renal fibrosis associated with two genetic mouse models, Am. J. Physiol., 285, F1060

Zeisberg, 2007, Endothelial-to-mesenchymal transition contributes to cardiac fibrosis, Nat. Med., 13, 952, 10.1038/nm1613

Zeisberg, 2007, Fibroblasts derive from hepatocytes in liver fibrosis via epithelial to mesenchymal transition, J. Biol. Chem., 282, 23337, 10.1074/jbc.M700194200

Zeisberg, 2008, Fibroblasts in kidney fibrosis emerge via endothelial-to-mesenchymal transition, J. Am. Soc. Nephrol., 19, 2282, 10.1681/ASN.2008050513

Zhan, 2006, Mullerian inhibiting substance regulates its receptor/SMAD signaling and causes mesenchymal transition of the coelomic epithelial cells early in Mullerian duct regression, Development, 133, 2359, 10.1242/dev.02383

Zhang, 2008, Vascular endothelial growth factor expression in peritoneal mesothelial cells undergoing transdifferentiation, Perit. Dial. Int., 28, 497, 10.1177/089686080802800513

Zohn, 2006, p38 and a p38-interacting protein are critical for downregulation of E-cadherin during mouse gastrulation, Cell, 125, 957, 10.1016/j.cell.2006.03.048