PMID- 9182671 OWN - NLM STAT- MEDLINE DCOM- 19970721 LR - 20190508 IS - 0021-9525 (Print) IS - 1540-8140 (Electronic) IS - 0021-9525 (Linking) VI - 137 IP - 6 DP - 1997 Jun 16 TI - The zinc-finger protein slug causes desmosome dissociation, an initial and necessary step for growth factor-induced epithelial-mesenchymal transition. PG - 1403-19 AB - 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. FAU - Savagner, P AU - Savagner P AD - Centre National de la Recherche Scientifique-Institut Curie, 75231 Paris Cedex 05, France. FAU - Yamada, K M AU - Yamada KM FAU - Thiery, J P AU - Thiery JP LA - eng SI - GENBANK/U97059 SI - GENBANK/U97060 SI - GENBANK/U97061 GR - 2R01 CA 490417-06/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Cell Biol JT - The Journal of cell biology JID - 0375356 RN - 0 (Cadherins) RN - 0 (DNA, Antisense) RN - 0 (DNA, Complementary) RN - 0 (RNA, Messenger) RN - 0 (SNAI1 protein, human) RN - 0 (Snai2 protein, mouse) RN - 0 (Snai2 protein, rat) RN - 0 (Snail Family Transcription Factors) RN - 0 (Transcription Factors) RN - 104781-85-3 (Fibroblast Growth Factor 1) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - 68238-35-7 (Keratins) SB - IM MH - Amino Acid Sequence MH - Animals MH - Base Sequence MH - Cadherins/metabolism MH - Cell Movement MH - Chickens MH - Cloning, Molecular MH - DNA, Antisense MH - DNA, Complementary MH - Desmosomes/drug effects/*physiology MH - Epithelium/drug effects MH - Fibroblast Growth Factor 1/*pharmacology MH - Gene Expression MH - Hepatocyte Growth Factor/*pharmacology MH - Humans MH - Keratins/metabolism MH - Mammals MH - Mesoderm/*physiology MH - Mice MH - Microscopy, Fluorescence MH - Molecular Sequence Data MH - Phenotype MH - RNA, Messenger MH - Rats MH - Sequence Analysis, DNA MH - Sequence Homology, Amino Acid MH - Snail Family Transcription Factors MH - Transcription Factors/genetics/*metabolism MH - Transfection MH - Tumor Cells, Cultured MH - Video Recording MH - *Zinc Fingers PMC - PMC2132541 EDAT- 1997/06/16 00:00 MHDA- 1997/06/16 00:01 PMCR- 1997/12/16 CRDT- 1997/06/16 00:00 PHST- 1997/06/16 00:00 [pubmed] PHST- 1997/06/16 00:01 [medline] PHST- 1997/06/16 00:00 [entrez] PHST- 1997/12/16 00:00 [pmc-release] AID - 10.1083/jcb.137.6.1403 [doi] PST - ppublish SO - J Cell Biol. 1997 Jun 16;137(6):1403-19. doi: 10.1083/jcb.137.6.1403.