The zinc-finger protein slug causes desmosome dissociation, an initial and necessary step for growth factor-induced epithelial-mesenchymal transition.
Epithelial-mesenchymal transition (EMT) is an essential morphogenetic process during embryonic development. It can be induced in vitro by hepatocyte growth factor/scatter factor (HGF/SF), or by FGF-1 in our NBT-II cell model for EMT. We tested for a central role in EMT of a zinc-finger protein called Slug. Slug mRNA and protein levels were increased transiently in FGF-1-treated NBT-II cells. Transient or stable transfection of Slug cDNA in NBT-II cells resulted in a striking disappearance of the desmosomal markers desmoplakin and desmoglein from cell-cell contact areas, mimicking the initial steps of FGF-1 or HGF/SF- induced EMT. Stable transfectant cells expressed Slug protein and were less epithelial, with increased cell spreading and cell-cell separation in subconfluent cultures. Interestingly, NBT-II cells transfected with antisense Slug cDNA were able to resist EMT induction by FGF-1 or even HGF/SF. This antisense effect was suppressed by retransfection with Slug sense cDNA. Our results indicate that Slug induces the first phase of growth factor-induced EMT, including desmosome dissociation, cell spreading, and initiation of cell separation. Moreover, the antisense inhibition experiments suggest that Slug is also necessary for EMT.
Savagner
P
P
Centre National de la Recherche Scientifique-Institut Curie, 75231 Paris Cedex 05, France.
Yamada
K M
KM
Thiery
J P
JP
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015820:Cadherins / Q000378:metabolism; D002465:Cell Movement; D002645:Chickens; D003001:Cloning, Molecular; D016373:DNA, Antisense; D018076:DNA, Complementary; D003896:Desmosomes / Q000187:drug effects / Q000502:physiology*; D004848:Epithelium / Q000187:drug effects; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology*; D015870:Gene Expression; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D007633:Keratins / Q000378:metabolism; D008322:Mammals; D008648:Mesoderm / Q000502:physiology*; D051379:Mice; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D010641:Phenotype; D012333:RNA, Messenger; D051381:Rats; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured; D014741:Video Recording; D016335:Zinc Fingers
D015820:Cadherins; D016373:DNA, Antisense; D018076:DNA, Complementary; D012333:RNA, Messenger; C000604407:SNAI1 protein, human; C000604449:Snai2 protein, mouse; C000604450:Snai2 protein, rat; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D016220:Fibroblast Growth Factor 1; D017228:Hepatocyte Growth Factor; D007633:Keratins