@article{17fc6d897a0644829579bbf353602672,
title = "A caveolin-dependent and PI3K/AKT-independent role of PTEN in β-catenin transcriptional activity",
abstract = "Loss of the tumour suppressor PTEN is frequent in human melanoma, results in MAPK activation, suppresses senescence and mediates metastatic behaviour. How PTEN loss mediates these effects is unknown. Here we show that loss of PTEN in epithelial and melanocytic cell lines induces the nuclear localization and transcriptional activation of β-catenin independent of the PI3K-AKT-GSK3β axis. The absence of PTEN leads to caveolin-1 (CAV1)-dependent β-catenin transcriptional modulation in vitro, cooperates with NRAS(Q61K) to initiate melanomagenesis in vivo and induces efficient metastasis formation associated with E-cadherin internalization. The CAV1-β-catenin axis is mediated by a feedback loop in which β-catenin represses transcription of miR-199a-5p and miR-203, which suppress the levels of CAV1 mRNA in melanoma cells. These data reveal a mechanism by which loss of PTEN increases CAV1-mediated dissociation of β-catenin from membranous E-cadherin, which may promote senescence bypass and metastasis. ",
keywords = "Animals, Blotting, Western, Cadherins/metabolism, Caveolin 1/genetics, Cell Line, Tumor, Feedback, Physiological, GTP Phosphohydrolases/genetics, Glycogen Synthase Kinase 3/metabolism, Glycogen Synthase Kinase 3 beta, Humans, Immunohistochemistry, Melanocytes/metabolism, Melanoma/genetics, Membrane Proteins/genetics, Mice, Mice, Transgenic, MicroRNAs, Microscopy, Fluorescence, PTEN Phosphohydrolase/genetics, Phosphatidylinositol 3-Kinases/metabolism, Prognosis, Proto-Oncogene Proteins c-akt/metabolism, Skin Neoplasms/genetics, Transcriptional Activation/genetics, beta Catenin/metabolism",
author = "Alejandro Conde-Perez and Gwendoline Gros and Christine Longvert and Malin Pedersen and Val{\'e}rie Petit and Zackie Aktary and Amaya Viros and Franck Gesbert and V{\'e}ronique Delmas and Florian Rambow and Bastian, {Boris C} and Campbell, {Andrew D} and Sophie Colombo and Isabel Puig and Alfonso Bellacosa and Owen Sansom and Richard Marais and {Van Kempen}, {Leon C L T} and Lionel Larue",
year = "2015",
month = aug,
day = "26",
doi = "10.1038/ncomms9093",
language = "English",
volume = "6",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}