Lebectin increases N-cadherin-mediated adhesion through PI3K/AKT pathway.
Cell adhesion molecules, including cadherins and integrins, play an essential role during tumor progression and represent potential targets for the development of new therapeutic agents. We previously showed that lebectin, a C-type lectin protein (CLP) issued from Macrovipera lebectina snake venom, inhibits integrin-mediated migration of IGR39 melanoma cells. Here we assessed whether lebectin modulates cell-cell adhesion. We demonstrated that lebectin promotes N-cadherin/catenin complex reorganization at cell-cell contacts, inducing a strengthening of intercellular adhesion. This reorganization is associated to phosphorylation of beta-catenin on tyrosine 142 residue. Interestingly, lebectin acts on N-cadherin-mediated cell-cell contacts through PI3K/Akt pathway. This effect could contribute to the blockage of tumor cell migration previously observed.
Sarray
Sameh
S
Institut Pasteur de Tunis, Tunis, Tunisia.
Siret
Carole
C
Lehmann
Maxime
M
Marrakchi
Naziha
N
Luis
José
J
El Ayeb
Mohamed
M
André
Frédéric
F
D015153:Blotting, Western; D015820:Cadherins / Q000187:drug effects* / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D037181:Lectins, C-Type; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D014757:Viper Venoms / Q000494:pharmacology*
D015820:Cadherins; D037181:Lectins, C-Type; D014757:Viper Venoms; C519594:lebectin protein, Macrovipera lebetina; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt