A caveolin-dependent and PI3K/AKT-independent role of PTEN in β-catenin transcriptional activity

• DOI: 10.1038/ncomms9093
• Publication Date: 2015-08-26T10:27:09Z
• Authors: Alejandro Conde-P...; Gwendoline Gros; Christine Longvert; Malin Pedersen; Valérie Petit; Zackie Aktary; Amaya Viros; Franck Gesbert; Véronique Delmas; Florian Rambow; Boris C. Bastian; Andrew D. Campbell; Sophie Colombo; Isabel Puig; Alfonso Bellacosa; Owen Sansom; Richard Marais; Leon C. L. T. Van...; Lionel Larue
• Keywords: Internalization

Abstract Loss of the tumour suppressor PTEN is frequent in human melanoma, results MAPK activation, suppresses senescence and mediates metastatic behaviour. How loss these effects unknown. Here we show that epithelial melanocytic cell lines induces nuclear localization transcriptional activation β-catenin independent PI3K–AKT–GSK3β axis. The absence leads to caveolin-1 (CAV1)-dependent modulation vitro , cooperates with NRAS Q61K initiate melanomagenesis vivo efficient metastasis formation associated E-cadherin internalization. CAV1-β–catenin axis mediated by a feedback loop which represses transcription miR-199a-5p miR-203 suppress levels CAV1 mRNA melanoma cells. These data reveal mechanism increases CAV1-mediated dissociation from membranous E-cadherin, may promote bypass metastasis.