IGF-II induces rapid beta-catenin relocation to the nucleus during epithelium to mesenchyme transition.
The epithelium to mesenchyme transition is thought to play a fundamental role during embryonic development and tumor progression. Loss of cell-cell adhesion and modification of both cell morphology and gene expression are the main events associated with this transition. There is a large amount of evidence suggesting that growth factors can initiate these events. Yet, the connection from growth factor induction to changes in cell adhesion and morphology is largely unknown. To elucidate this connection, we have investigated the action of IGF-II on E-cadherin/beta-catenin complex-mediated cell-cell adhesion and on beta-catenin/TCF-3 mediated gene expression. We can show that (1) IGF-II induces a rapid epithelium to mesenchymal transition; (2) IGF1R, the receptor for IGF-II, belongs to the same membrane complex as E-cadherin and beta-catenin; (3) IGF-II induces a redistribution of beta-catenin from the plasma membrane to the nucleus and an intracellular sequestration and degradation of E-cadherin; (4) IGF-II induces the transcription of beta-catenin/TCF-3 target genes. Based on the given case of IGF-II and E-cadherin/beta-catenin complex, this study reveals the backbone of a cascade connecting growth factor signaling with cell-cell adhesion during EMT.
Morali
O G
OG
Developmental Genetics of Melanocytes, UMR 146 CNRS-Institut Curie, Bat. 110, 91405, Orsay Cedex, France.
Delmas
V
V
Moore
R
R
Jeanney
C
C
Thiery
J P
JP
Larue
L
L
D016475:3T3 Cells; D021581:Active Transport, Cell Nucleus; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D019938:Cyclin D1 / Q000096:biosynthesis / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004848:Epithelium / Q000196:embryology*; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology*; D046911:Macromolecular Substances; D008648:Mesoderm / Q000166:cytology*; D051379:Mice; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D015534:Trans-Activators; D014407:Tumor Cells, Cultured; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; D015820:Cadherins; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D046911:Macromolecular Substances; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D015534:Trans-Activators; D051176:beta Catenin; D019938:Cyclin D1; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1