162 Cell 145, April 1, 2011 ©2011 Elsevier Inc. DOI 10.1016/j.cell.2011.03.029 See online version for legend and references. SnapShot: The Epithelial-Mesenchymal Transition Jonathan P. Sleeman 3,4 and Jean Paul Thiery 2,3 1 IMCB and Experimental Therapeutics Centre, Biopolis A*STAR, 138673 Singapore; 2 Cancer Science Institute, 117456 Singapore 3 University of Heidelberg, Medical Faculty Mannheim, D-68167 Mannheim, Germany; 4 Karlsruhe Institute of Technology, Postfach 3640, 76021 Karlsruhe, Germany Laminin 5 TβRI TβRI TβRII Snail1/2 Zeb1/2 Par3 Par6 aPKC BMPs BMPR1 BMPR2 Patched Growth factors IL-6 JAG2 JAM p120-Cat p53 RhoA Cdc42 RhoA RhoA PDGF Cdc42 Cdc42 Glu-tubulin Rac1 Par6 Par3 aPKC Claudin JAM Occludin Claudin Occludin ZO3 ZO1 ZO2 Actin IQGAP E-cadherin Nectin β-cat β-cat β-cat β-cat β-cat β-cat Afadin F-actin Vinculin X α-Actinin Clip170 Dynein/ dynactin complex miR-200 FOXA1/2 BASEMENT MEMBRANE ROCK DDR1 Collective cell migration p190 Rho GAP DAP21P GSK3β RhoA RhoE Myosin light chain HIF 1/2 LoxL2 E2.2 KLF8 FOXQ1 E47 GSC Twist Snail1/2 Snail1/2 Smad2/3 Hedgehog ER PAK1 STAT3 IL-6R PI3K Ras RTK LIV1 AKT MAPK NF-κB NF-κB CSL Gli1 MTA3 Zeb1/2 miR-205 miR-200 miR-205 E-cadherin and other downregulated genes (see box A) Upregulated genes (see box B) E-cadherin Desmosome Cytokeratin Gap junction Plakoglobin Desmoplakin Balanced activities Tight junction EPITHELIAL MESENCHYM MESENCHYMAL Adherens junction Stabilized actin cytoskeleton Apicobasal microtubules p120-Cat p120-Cat Kaiso p120-Cat p120-Cat GSK3β Dishevelled LRP5/6 Frizzled Nectin Afadin RTK DDR1 Collagen 1 MMPs NCAM N-cad PDGFR Transcription Focal adhesion formation Adherens junction disassembly Filopodia Lamellipodia Migration Invasion ECM remodelling Focal adhesion assembly and turnover Examples of up- regulated genes TβRI Vimentin SMA N-cadherin NCAM Fibronectin Laminins miR-661 MMPs Examples of down- regulated genes Tubulin tyrosine ligase Claudins Occludins ZO1/ZO3 Crumbs3 Desmoplakin Connexin43 E-cadherin Nectin-1 VE-cadherin Cytokeratins Collagen I, II Other EMT-associated effects Resistance to senescence Resistance to apoptosis Therapy resistance Stemness Cytoskeleton remodeling Membrane ruffles Loss of desmosomes Microtentacles Dissociation of tight junctions Loss of gap junctions Endocytosis degradation Focal adhesion formation Increased TGF-β signaling E-cadherin degradation Basement membrane degradation EB1 Ninein p190 Rho GAP p190 Rho GAP Smurf1 α-cat Rap1 FAK FAK FAK Fyn Rac1b Hypoxia Rac1 Rac1 Reactive oxygen species Pyk2 ILK AKT DAB2 p130 CAS α-cat A B Other EMT-inducing pathways ILEI Endothelin-A receptor-PI3K TNF-α-NF-κB, Akt Hyaluronic acid COX2-PGE2 AMF PTH(rP)R Bile acids Nicotine UV irradiation SCF Axl-Gas6 Plectin Wnt FAK Hakai RhoA Proteasome CK1 E Par3 Par6 c-src c-src ZO3 ZO1 ZO2 Myosin light chain Desmosome P Smad2/3 P Snail1/2 P Proteasome Proteasome Proteasome Proteasome Proteasome Proteasome Proteasome P -cat CK1 β -cat P Ub RhoA Snail1/2 RhoA Proteasome Proteasome Proteasome Ub FAK ILK P P Fyn Fyn P T β β β RI T β RII aPKC Par3 Par6 P β -cat c-src P Integrin α6β4 Integrin α6β4 Desmoglein Desmoglein Desmocollin Desmocollin NOTCH NOTCH Smoothened Smoothened TGF-β TGF-β Six1