Dataset Information

A caveolin-dependent and PI3K/AKT-independent role of PTEN in ?-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 ?-catenin independent of the PI3K-AKT-GSK3? axis. The absence of PTEN leads to caveolin-1 (CAV1)-dependent ?-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-?-catenin axis is mediated by a feedback loop in which ?-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 ?-catenin from membranous E-cadherin, which may promote senescence bypass and metastasis.

SUBMITTER: Conde-Perez A

PROVIDER: S-EPMC4560817 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Conde-Perez Alejandro A Gros Gwendoline G Longvert Christine C Pedersen Malin M Petit Valérie V Aktary Zackie Z Viros Amaya A Gesbert Franck F Delmas Véronique V Rambow Florian F Bastian Boris C BC Campbell Andrew D AD Colombo Sophie S Puig Isabel I Bellacosa Alfonso A Sansom Owen O Marais Richard R Van Kempen Leon C L T LC Larue Lionel L

Nature communications 20150826

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, coopera ...[more]

PMID: 26307673

Similar Datasets

Project description:Lung cancer is the most prevalent in cancer-related deaths, while breast carcinoma is the second most dominant cancer in women, accounting for the most number of deaths worldwide. Cancers are heterogeneous diseases that consist of several subtypes based on the presence or absence of hormone receptors and human epidermal growth factor receptor 2. Several drugs have been developed targeting cancer biomarkers; nonetheless, their efficiency are not adequate due to the high reemergence rate of cancers and fundamental or acquired resistance toward such drugs, which leads to partial therapeutic possibilities. Recent studies on cardiac glycosides (CGs) positioned them as potent cytotoxic agents that target multiple pathways to initiate apoptosis and autophagic cell death in many cancers. In the present study, our aim is to identify the anticancer activity of a naturally available CG (strophanthidin) in human breast (MCF-7), lung (A549), and liver cancer (HepG2) cells. Our results demonstrate a dose-dependent cytotoxic effect of strophanthidin in MCF-7, A549, and HepG2 cells, which was further supported by DNA damage on drug treatment. Strophanthidin arrested the cell cycle at the G2/M phase; this effect was further validated by checking the inhibited expressions of checkpoint and cyclin-dependent kinases in strophanthidin-induced cells. Moreover, strophanthidin inhibited the expression of several key proteins such as MEK1, PI3K, AKT, mTOR, Gsk3α, and β-catenin from MAPK, PI3K/AKT/mTOR, and Wnt/β-catenin signaling. The current study adequately exhibits the role of strophanthidin in modulating the expression of various key proteins involved in cell cycle arrest, apoptosis, and autophagic cell death. Our in silico studies revealed that strophanthidin can interact with several key proteins from various pathways. Taken together, this study demonstrates the viability of strophanthidin as a promising anticancer agent, which may serve as a new anticancer drug.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets