EMTincancer课件.pptVIP

EMT and Cancer Subtitle: Be Good to your Cadherins Epithelial Cells Mesenchymal Cells: Junctions Complex, stable Looser or none Tissue Uniform array, continuous layer No uniform tissue structure Polarity Apical vs. Basal Leading vs. Trailing edge Motility Lack of mobility by individual cells Motile, potentially invasive Adhesion NIH3T3 Strong, stable E-cadherin based Loose, transient N-cadherin based MDCK Polarity Columnar Epithelium Migrating Fibroblast Motility Lecuit Pilot, Nature Cell Biology 5, 103 - 108 (2003) What is EMT? EMT in Development Implies a comprehensive and coordinated change of fate and/or function. EMT in the Adult What is it? Loss of E-cadherin Increased migratory/invasive behavior Loss of Epithelial characteristics Fibroblastoid Morphology Does it exist? Depends on your definition Mixed lineage markers Where is it important? Wound Repair Fibrosis Metastasis Steps in Malignant Progression Metastatic Growth in the Liver 90% human cancer is epithelial in origin Metastasis-associated tumorigenesis accounts for 90% of cancer deaths Metastasis 4. Increases in extracellular proteolytic activity 5. Proliferative 1. Complete EMT A process wherein static epithelial cells: 1. Loose cell-cell contacts 2. Acquire mesenchymal morphology 3. Manifest a migratory phenotype Functional Definition of EMT 2. Incomplete EMT A transition involving less then the complete set, but still may have significant ramifications on the functioning of the cell population. ? Virtually all carcinomas will retain significant expression of epithelial markers, while simultaneously losing key epithelial determinants and inappropriately expressing mesenchymal markers, so EMT-like may be a better term. Proteins that increase in abundance N-cadherin Snail1 (Snail) Snail2 (Slug) Twist MMP-2 MMP-3 MMP-9 Vimentin Integrin {alpha}v?6 Fibronectin Goose