E-cadherin, beta-catenin, and ZEB1 in malignant progression of cancer.
The embryonic program 'epithelial-mesenchymal transition' (EMT) is activated during tumor invasion in disseminating cancer cells. Characteristic to these cells is a loss of E-cadherin expression, which can be mediated by EMT-inducing transcriptional repressors, e.g. ZEB1. Consequences of a loss of E-cadherin are an impairment of cell-cell adhesion, which allows detachment of cells, and nuclear localization of beta-catenin. In addition to an accumulation of cancer stem cells, nuclear beta-catenin induces a gene expression pattern favoring tumor invasion, and mounting evidence indicates multiple reciprocal interactions of E-cadherin and beta-catenin with EMT-inducing transcriptional repressors to stabilize an invasive mesenchymal phenotype of epithelial tumor cells.
Schmalhofer
Otto
O
Department of Visceral Surgery, University of Freiburg, Hugstetter Strasse 55, 79106, Freiburg, Germany.
Brabletz
Simone
S
Brabletz
Thomas
T
D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion; D018450:Disease Progression; D004848:Epithelium / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D008648:Mesoderm / Q000378:metabolism; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D000071799:Zinc Finger E-box-Binding Homeobox 1; D051176:beta Catenin / Q000378:metabolism*
D015820:Cadherins; D018398:Homeodomain Proteins; D014157:Transcription Factors; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; D051176:beta Catenin