Compartmentalization in membrane rafts defines a pool of N-cadherin associated with catenins and not engaged in cell-cell junctions in melanoma cells.
Melanoma progression is associated with changes in adhesion receptor expression, in particular upregulation of N-cadherin which promotes melanoma cell survival and invasion. Plasma membrane lipid rafts contribute to the compartmentalization of signaling complexes thereby regulating their function, but how they may affect the properties of adhesion molecules remains elusive. In this study, we addressed the question whether lipid rafts in melanoma cells may contribute to the compartmentalization of N-cadherin. We show that a fraction of N-cadherin in a complex with catenins is associated with cholesterol/sphingolipid-rich membrane microdomains in aggressive melanoma cells in vitro and experimental melanomas in vivo. Partitioning of N-cadherin in membrane rafts is not modulated by growth factors and signaling pathways relevant to melanoma progression, is not necessary for cell-cell junctions' establishment or maintenance, and is not affected by cell-cell junctions' and actin cytoskeleton disruption. These results reveal that two independent pools of N-cadherin exist on melanoma cell surface: one pool is independent of lipid rafts and is engaged in cell-cell junctions, while a second pool is localized in membrane rafts and does not participate in cell-cell adhesions. Targeting to membrane rafts may represent a previously unrecognized mechanism regulating N-cadherin function in melanoma cells.
Division of Experimental Oncology, Centre Pluridisciplinaire d'Oncologie, Lausanne Cancer Center and Swiss Institute for Experimental Cancer Research, CH-1066 Epalinges s/Lausanne, Switzerland.
Laetitia
L
Rossier-Pansier
Frédérique
F
Baruthio
Curzio
C
Rüegg
Agnese
A
Mariotti
D015820:Cadherins / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D051177:Catenins / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002450:Cell Communication; D002451:Cell Compartmentation; D045744:Cell Line, Tumor; D018450:Disease Progression; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods; D007365:Intercellular Junctions / Q000378:metabolism* / Q000473:pathology; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D021962:Membrane Microdomains / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D025941:Protein Interaction Mapping / Q000379:methods; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D051176:beta Catenin / Q000378:metabolism; D000095002:Delta Catenin
D015820:Cadherins; D002352:Carrier Proteins; D051177:Catenins; D015815:Cell Adhesion Molecules; D010750:Phosphoproteins; D051176:beta Catenin; D000095002:Delta Catenin