Cytoplasmic redistribution of E-cadherin-catenin adhesion complex is associated with down-regulated tyrosine phosphorylation of E-cadherin in human bronchopulmonary carcinomas.
The E-cadherin-catenin complex, by mediating intercellular adhesion, regulates the architectural integrity of epithelia. Down-regulation of its expression is thought to contribute to invasion of carcinoma cells. To investigate the involvement of the E-cadherin-catenin adhesion system in the progression of human bronchopulmonary carcinomas, we compared the immunohistochemical distribution of E-cadherin, alpha-catenin, and beta-catenin in four human bronchial cancer cell lines with different invasive abilities and in 44 primary bronchopulmonary tumors. Although invasive bronchial cell lines did not express E-cadherin and alpha-catenin, complete down-regulation of cadherin-catenin complex expression was a rare event in vivo in bronchopulmonary carcinomas. Nevertheless, a spotty and cytoplasmic pattern of E-cadherin and catenins was observed in 32 primary tumors, only in invasive tumor clusters. Immunoprecipitation experiments showed that this redistribution was not related to a disruption of cadherin-catenin interaction but to down-regulated tyrosine phosphorylation of E-cadherin. We conclude that loss of E-cadherin and/or catenins is not a prominent early event in the invasive progression of human bronchopulmonary carcinomas in vivo. The decreased tyrosine phosphorylation of E-cadherin may reflect a loss of functionality of the complex and implicates a major role in tumor invasion.
Nawrocki
B
B
INSERM U.314, IFR 53, Unité de Biologie Cellulaire, Laboratoire Pol Bouin, CHU, Reims, France. birembau@centre02-univ-reims.fr
Polette
M
M
Van Hengel
J
J
Tournier
J M
JM
Van Roy
F
F
Birembault
P
P
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D015820:Cadherins / Q000378:metabolism*; D002283:Carcinoma, Bronchogenic / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D015536:Down-Regulation; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D046911:Macromolecular Substances; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D015534:Trans-Activators; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism*; D051178:alpha Catenin; D051176:beta Catenin
C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D046911:Macromolecular Substances; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D014443:Tyrosine