Role of the E-cadherin/alpha-catenin complex in modulating cell-cell and cell-matrix adhesive properties of invasive colon carcinoma cells.
BACKGROUND
The clinical behavior of colorectal cancer depends on its ability to invade and metastasize. Metastatic cells must dissociate from other cells and invade through basement membrane and stroma. Cell-cell adhesion in epithelial cells is mediated by the cell surface protein E-cadherin in association with alpha- and beta-catenin, which link E-cadherin to the cytoskeleton. Decreased cell-cell adhesion and increased motility on laminin have been correlated with more poorly differentiated and aggressive carcinomas.


METHODS
In this study, the RKO cell line, previously shown by us to lack E-cadherin expression, was transfected with the complementary DNA for E-cadherin. The transfectants were selected for high levels of surface expression by sequential FACS and examined in functional assays.


RESULTS
In comparison to control transfectants, the E-cadherin transfectants exhibited a more epithelial-like morphology, a 30% increase in Ca(2+)-dependent cell-cell aggregation, and a markedly reduced motility on the matrix proteins, collagen I and laminin.


CONCLUSIONS
These data demonstrate that correction of a defect in the cadherin/catenin cell-cell adhesion complex, often found in poorly differentiated and highly invasive tumors, facilitates increased cell-cell adhesion and retards tumor cell migration on basement membrane and stromal proteins.
D001485:Basement Membrane / Q000378:metabolism / Q000473:pathology; D015820:Cadherins / Q000235:genetics / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion; D002449:Cell Aggregation; D002465:Cell Movement; D003094:Collagen / Q000378:metabolism; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D003598:Cytoskeletal Proteins / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007797:Laminin / Q000378:metabolism; D009361:Neoplasm Invasiveness; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology; D051178:alpha Catenin
C495273:CTNNA1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D007797:Laminin; D051178:alpha Catenin; D003094:Collagen; D002118:Calcium