Simultaneous expression of caveolin-1 and E-cadherin in ovarian carcinoma cells stabilizes adherens junctions through inhibition of src-related kinases.
Cadherin-mediated adhesion plays an important role in maintaining cell-cell contacts and reducing tumor metastasis. However, neo-expression of E-cadherin in ovarian carcinoma does not prevent the release and spread of cells from the primary tumor. Because caveolin-1 is down-regulated concomitantly with E-cad expression, we investigated whether the stability of adherens junctions in ovarian carcinoma was affected by caveolin-1 expression. We used IGROV1 cells transfected with caveolin-1 (IGtC3), mock-transfected control cells (IGtM87), and SKOV3 cells that endogenously express caveolin-1. Simultaneous expression of caveolin-1 and E-cadherin favored membrane distribution of E-cadherin and its associated catenin (p120ctn), even when caveolin-1 was only focally associated with adherens junctions. Silencing of caveolin-1 induced intracellular E-cadherin redistribution in IGtC3 and SKOV3 cells. Treatment with the specific src kinase inhibitor PP1 increased E-cadherin expression in IGtM87 and SKOV3 cells and enhanced membrane localization of both E-cadherin and p120ctn. However, PP1 could not completely reverse the detrimental effects on cell-cell adhesion induced by Ca2+ depletion in IGtM87 cells. Together, our data suggest that caveolin-1 expression indirectly promotes cell-cell adhesion in ovarian carcinoma cells by a mechanism involving inhibition of src-related kinases. Thus, down-regulation or loss of caveolin-1 might contribute significantly to the spread of tumor cells from the primary tumor.
Miotti
Silvia
S
Unit of Molecular Therapies, Department of Experimental Oncology, Istituto Nazionale Tumori, Via Venezian 1, 20133 Milan, Italy. silvia.miotti@istitutotumori.mi.it
Tomassetti
Antonella
A
Facetti
Ileana
I
Sanna
Elena
E
Berno
Valeria
V
Canevari
Silvana
S
D022005:Adherens Junctions / Q000235:genetics / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western; D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics; D002118:Calcium / Q000378:metabolism; D051177:Catenins; D051242:Caveolin 1 / Q000096:biosynthesis* / Q000235:genetics; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000032:analysis; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000737:chemistry; D004591:Electrophoresis, Polyacrylamide Gel; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D020868:Gene Silencing; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D021962:Membrane Microdomains / Q000737:chemistry; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000648:ultrastructure*; D010750:Phosphoproteins / Q000032:analysis; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D014162:Transfection; D019061:src-Family Kinases / Q000037:antagonists & inhibitors; D000095002:Delta Catenin
C108123:4-amino-5-(4-methylphenyl)-7-(tert-butyl)pyrazolo(3,4-d)pyrimidine; D015820:Cadherins; D051177:Catenins; D051242:Caveolin 1; D015815:Cell Adhesion Molecules; D004791:Enzyme Inhibitors; D010750:Phosphoproteins; D011720:Pyrazoles; D011743:Pyrimidines; D019061:src-Family Kinases; D002118:Calcium; D000095002:Delta Catenin; C000722347:CTNND1 protein, human