Ether lipid 1-O-octadecyl-2-O-methyl-3-glycero-phosphocholine inhibits cell-cell adhesion through translocation and clustering of E-cadherin and episialin in membrane microdomains.
The ether lipid 1-O-octadecyl-2-O-methyl-3-glycero-phosphocholine (ET-18-OMe) inhibits cell-cell adhesion and induces invasiveness of breast cancer cells. Previously, we showed that a loss of cell-cell adhesion was due to sterical hindrance of E-cadherin by the anti-adhesive properties of the cell surface mucin episialin. Here, we demonstrated that the ether lipid ET-18-OMe induced the translocation of E-cadherin and episialin to membrane microdomains, enriched in glycosphingolipids, known to be involved in cell-cell adhesion and cell signaling. In addition, it was found that E-cadherin and clusters of episialin colocalized and associated with the glycosphingolipid, MSGb5, upon treatment with ET-18-OMe. Together, these results suggest that ET-18-OMe inhibits cell-cell adhesion by inducing the translocation of E-cadherin and episialin into MSGb5-enriched membrane microdomains, which leads to clustering and colocalization of the pro-adhesive E-cadherin and the anti-adhesive episialin thereby inhibiting cell-cell adhesion.
Van Slambrouck
Severine
S
Laboratory of Biochemical and Biomedical Research, Department of Chemistry, New Mexico Tech, Socorro, NM 87801, USA.
Hilkens
John
J
Steelant
Wim F A
WF
D000970:Antineoplastic Agents / Q000494:pharmacology*; D015820:Cadherins / Q000187:drug effects* / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects*; D002450:Cell Communication / Q000187:drug effects; D045744:Cell Line, Tumor; D005455:Fluorescent Antibody Technique; D006028:Glycosphingolipids / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D021962:Membrane Microdomains / Q000187:drug effects* / Q000378:metabolism; D018396:Mucin-1 / Q000187:drug effects* / Q000378:metabolism; D010742:Phospholipid Ethers / Q000494:pharmacology*; D021381:Protein Transport / Q000187:drug effects
D000970:Antineoplastic Agents; D015820:Cadherins; D006028:Glycosphingolipids; D018396:Mucin-1; D010742:Phospholipid Ethers; C026659:edelfosine