Source: Annual Congress 2013 –Novel in vitro and animal models to study lung diseases

Abstract

Rationale: Transforming growth factor beta (TGFbeta)-induced translocation of beta-catenin into cytoplasm is a critical step to induce de novo transcription of epithelial-mesenchymal transition (EMT) target genes. Although we demonstrate that modulation of phosphorylation sites in the PTEN C-terminus blunt TGFbeta-induced EMT in lung cancers, whether TGFbeta can induce translocation of beta-catenin via phosphorylation of the PTEN C-terminal tail remains elusive.
Objective: We determined the underlying mechanisms, by which modulation of phosphorylation sites in the PTEN C-terminus tail could rescue EMT.
Methods: Immunofluorescence of beta-catenin was performed for the lung cancer cells with mutation of phosphorylation sites in the PTEN C-terminal tail (PTEN4A).
Main Results: H358ON cells with either GFP or GFP-PTENWt protein showed TGFbeta-induced beta-catenin translocation into the cytoplasm when treated by Doxycycline. In contrats, only de novo GFP-PTEN4A protein completely inhibited beta-catenin translocation induced by TGFbeta stimulation. This finding was supported by the data that ectopic PTEN4A, not PTENWt, protein in H1299 cells completely inhibited beta-catenin translocation induced by TGFbeta stimulation.
Conclusion: Our data suggest that modulation of phosphorylation sites in the PTEN C-terminus inhibits TGFbeta-induced EMT via blockade of beta-catenin translocation. Our study is first to demonstrate the underlying mechanisms, by which phosphorylation sites in the PTEN C-terminal tail might be a promising therapeutic target to negatively regulate TGFbeta-induced EMT in lung cancers.

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Citations should be made in the following way:
N. Hashimoto, D. Aoyama, M. Kusumose, Y. Hasegawa (Nagoya, Japan). Translocation of beta-catenin into cytoplasm during TGFbeta-induced EMT is negatively regulated by phosphorylation of the PTEN C-terminus in lung cancers. Eur Respir J 2013; 42: Suppl. 57, 519

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