E-Cadherin mediates MMP down-regulation in highly invasive bronchial tumor cells.
The disorganization of E-cadherin/catenin complexes and the overexpression of matrix metalloproteinases (MMPs) are frequently involved in the capacity of epithelial cells to acquire an invasive phenotype. The functional link between E-cadherin and MMPs was studied by transfecting invasive bronchial BZR tumor cells with human E-cadherin cDNA. Using different in vitro (cell dispersion, modified Boyden chamber) and in vivo assays (human airway epithelial xenograft), we showed that E-cadherin-positive clones displayed a decrease of invasive abilities. As shown by immunoprecipitation, the re-expressed E-cadherin was able to sequestrate one part of free cytoplasmic beta-catenin in BZR cells. The decrease of beta-catenin transcriptional activity in E-cadherin-transfected clones was demonstrated using the TOP-FLASH reporter construct. Finally, we observed a decrease of MMP-1, MMP-3, MMP-9, and MT1-MMP, both at the mRNA and at the protein levels, in E-cadherin-positive clones whereas no changes in MMP-2, TIMP-1, or TIMP-2 were observed when compared with control clones. Moreover, zymography analysis revealed a loss of MMP-2 activation ability in E-cadherin-positive clones treated with the concanavalin A lectin. These data demonstrate a direct role of E-cadherin/catenin complex organization in the regulation of MMPs and suggest an implication of this regulation in the expression of an invasive phenotype by bronchial tumor cells.
Nawrocki-Raby
Béatrice
B
Institut National de la Santé et de la Recherche Mèdicale (INSERM) Unité Mixte de Recherche Santé (UMRS) 514, Laboratoire Pol Bouin, Reims, France. beatrice.raby@univ-reims.fr
Gilles
Christine
C
Polette
Myriam
M
Martinella-Catusse
Corinne
C
Bonnet
Noël
N
Puchelle
Edith
E
Foidart
Jean-Michel
JM
Van Roy
Frans
F
Birembaut
Philippe
P
D000818:Animals; D001984:Bronchial Neoplasms / Q000378:metabolism* / Q000473:pathology*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D017930:Genes, Reporter; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051379:Mice; D009361:Neoplasm Invasiveness; D051381:Rats; D017208:Rats, Wistar; D020545:Respiratory Mucosa / Q000378:metabolism / Q000473:pathology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D014183:Transplantation, Heterologous; D051176:beta Catenin
C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D015820:Cadherins; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin; D020782:Matrix Metalloproteinases