L-CAM expression induces fibroblast-epidermoid transition in squamous carcinoma cells and down-regulates the endogenous N-cadherin.
SCC9 cells, derived from a squamous carcinoma of the tongue, were shown to lack E-cadherin but express alpha- and beta-catenins and N-cadherin. These cells also lack plakoglobin expression, do not assemble desmosomes and exhibit the typical morphology and growth properties of transformed cells. The N-cadherin expressed in SCC9 cells has properties similar to other classical cadherins, including interactions with the catenins. We transfected SCC9 cells with a full-length cDNA for L-CAM (liver cell adhesion molecule), the functional chicken homologue of E-cadherin. The exogenously expressed L-CAM formed complexes with catenins and the cytoskeleton and induced a morphological transition from fibroblastoid to epithelioid, conferred density-dependent growth inhibition, increased aggregation ability, and increased synthesis and stability of alpha- and beta-catenins. Coincident with these phenotypic changes, we detected a significant reduction in the level of endogenous N-cadherin, primarily as a result of rapid degradation of this protein in L-CAM-expressing cells. These results show the abnormal expression of N-cadherin in these transformed epidermoid cells, demonstrate the dynamics of the relationship between two cadherins, and provide a model system for the functional analysis of the tumor suppressor activity of E-cadherin in carcinomas.
Li
Z
Z
Department of Cell Biology, University of Alberta, Edmonton, Alberta, Canada, T6G 2H7.
Gallin
W J
WJ
Lauzon
G
G
Pasdar
M
M
D015820:Cadherins / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology*; D002455:Cell Division; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D015536:Down-Regulation; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism / Q000473:pathology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D046911:Macromolecular Substances; D010641:Phenotype; D014062:Tongue Neoplasms; D015534:Trans-Activators; D014407:Tumor Cells, Cultured; 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