The transcription factor snail induces tumor cell invasion through modulation of the epithelial cell differentiation program.
Abberant activation of the process of epithelial-mesenchymal transition in cancer cells is a late event in tumor progression. A key inducer of this transition is the transcription factor Snail, which represses E-cadherin. We report that conditional expression of the human transcriptional repressor Snail in colorectal cancer cells induces an epithelial dedifferentiation program that coincides with a drastic change in cell morphology. Snail target genes control the establishment of several junctional complexes, intermediate filament networks, and the actin cytoskeleton. Modulation of the expression of these genes is associated with loss of cell aggregation and induction of invasion. Chromatin immunoprecipitation experiments showed that repression of selected target genes is associated with increased binding of Snail to their promoters, which contain consensus Snail-binding sites. Thus, Snail constitutes a master switch that directly represses the epithelial phenotype, resulting in malignant carcinoma cells.
De Craene
Bram
B
Unit of Molecular and Cellular Oncology, Department for Molecular Biomedical Research, VIB-Ghent University, Belgium.
Gilbert
Barbara
B
Stove
Christophe
C
Bruyneel
Erik
E
van Roy
Frans
F
Berx
Geert
G
D000199:Actins / Q000235:genetics / Q000378:metabolism; D002449:Cell Aggregation / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000473:pathology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009361:Neoplasm Invasiveness; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
D000199:Actins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors