Regulation of Snail transcription during epithelial to mesenchymal transition of tumor cells.
Expression of Snail transcriptional factor is a determinant in the acquisition of a mesenchymal phenotype by epithelial tumor cells. However, the regulation of the transcription of this gene is still unknown. We describe here the characterization of a human SNAIL promoter that contains the initiation of transcription and regulates the expression of this gene in tumor cells. This promoter was activated in cell lines in response to agents that induce Snail transcription and the mesenchymal phenotype, as addition of the phorbol ester PMA or overexpression of integrin-linked kinase (ILK) or oncogenes such as Ha-ras or v-Akt. Although other regions of the promoter were required for a complete stimulation by Akt or ILK, a minimal fragment (-78/+59) was sufficient to maintain the mesenchymal specificity. Activity of this minimal promoter and SNAIL RNA levels were dependent on ERK signaling pathway. NFkappaB/p65 also stimulated SNAIL transcription through a region located immediately upstream the minimal promoter, between -194 and -78. These results indicate that Snail transcription is driven by signaling pathways known to induce epithelial to mesenchymal transition, reinforcing the role of Snail in this process.
Barberà
Maria José
MJ
Unitat de Biologia Cel.lular i Molecular, Institut Municipal d'Investigació Mèdica, Universitat Pompeu Fabra, Barcelona, Spain.
Puig
Isabel
I
Domínguez
David
D
Julien-Grille
Sylvia
S
Guaita-Esteruelas
Sandra
S
Peiró
Sandra
S
Baulida
Josep
J
Francí
Clara
C
Dedhar
Shoukat
S
Larue
Lionel
L
García de Herreros
Antonio
A
D002454:Cell Differentiation; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics*; D004847:Epithelial Cells / Q000166:cytology*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D008648:Mesoderm / Q000166:cytology*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics*; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors