Involvement of TGFβ-induced phosphorylation of the PTEN C-terminus on TGFβ-induced acquisition of malignant phenotypes in lung cancer cells
| Autor: | Kazuyoshi Imaizumi, Naozumi Hashimoto, Koji Sakamoto, Masaaki Kusunose, Yoshinori Hasegawa, Motohiro Kimura, Ryo Ogata, Tsutomu Kawabe, Takashi Kohnoh, Daisuke Aoyama |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Epithelial-Mesenchymal Transition
Lung Neoplasms Phosphatase Gene Expression lcsh:Medicine Chromosomal translocation Smad Proteins Biology Mice Cell Movement Transforming Growth Factor beta Cell Line Tumor Tensin PTEN Animals Humans Protein Interaction Domains and Motifs Phosphorylation lcsh:Science Cell Proliferation Tumor microenvironment Multidisciplinary lcsh:R PTEN Phosphohydrolase Tumor Burden Disease Models Animal Phenotype Focal Adhesion Kinase 1 Mutation Cancer research biology.protein Heterografts lcsh:Q Signal transduction Transforming growth factor Signal Transduction Research Article |
| Zdroj: | PLoS ONE, Vol 8, Iss 11, p e81133 (2013) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Transforming growth factor β (TGFβ) derived from the tumor microenvironment induces malignant phenotypes such as epithelial-mesenchymal transition (EMT) and aberrant cell motility in lung cancers. TGFβ-induced translocation of β-catenin from E-cadherin complexes into the cytoplasm is involved in the transcription of EMT target genes. PTEN (phosphatase and tensin homologue deleted from chromosome 10) is known to exert phosphatase activity by binding to E-cadherin complexes via β-catenin, and recent studies suggest that phosphorylation of the PTEN C-terminus tail might cause loss of this PTEN phosphatase activity. However, whether TGFβ can modulate both β-catenin translocation and PTEN phosphatase activity via phosphorylation of the PTEN C-terminus remains elusive. Furthermore, the role of phosphorylation of the PTEN C-terminus in TGFβ-induced malignant phenotypes has not been evaluated. To investigate whether modulation of phosphorylation of the PTEN C-terminus can regulate malignant phenotypes, here we established lung cancer cells expressing PTEN protein with mutation of phosphorylation sites in the PTEN C-terminus (PTEN4A). We found that TGFβ stimulation yielded a two-fold increase in the phosphorylated -PTEN/PTEN ratio. Expression of PTEN4A repressed TGFβ-induced EMT and cell motility even after snail expression. Our data showed that PTEN4A might repress EMT through complete blockade of β-catenin translocation into the cytoplasm, besides the inhibitory effect of PTEN4A on TGFβ-induced activation of smad-independent signaling pathways. In a xenograft model, the tumor growth ratio was repressed in cells expressing PTEN4A. Taken together, these data suggest that phosphorylation sites in the PTEN C-terminus might be a therapeutic target for TGFβ-induced malignant phenotypes in lung cancer cells. |
| Databáze: | OpenAIRE |
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