TOPK/PBK promotes cell migration via modulation of the PI3K/PTEN/AKT pathway and is associated with poor prognosis in lung cancer
| العنوان: | TOPK/PBK promotes cell migration via modulation of the PI3K/PTEN/AKT pathway and is associated with poor prognosis in lung cancer |
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| المؤلفون: | Chen Jy, Yu Chung Wu, Yi Hua Jan, Yang Bm, Michael Hsiao, Shih Mc, Jin Mei Lai, Ming Shyan Huang, Pei Jung Lu, Hsiu Chi Cheng, Chih Jen Yang |
| المصدر: | Oncogene. 31:2389-2400 |
| بيانات النشر: | Springer Science and Business Media LLC, 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Male, Cancer Research, Lung Neoplasms, Adenocarcinoma, Biology, Disease-Free Survival, Metastasis, Phosphatidylinositol 3-Kinases, Cell Movement, Cell Line, Tumor, Genetics, medicine, Humans, Tensin, PTEN, Neoplasm Invasiveness, Neoplasm Metastasis, Phosphorylation, RNA, Small Interfering, Lung cancer, Molecular Biology, Protein kinase B, PI3K/AKT/mTOR pathway, Aged, Mitogen-Activated Protein Kinase Kinases, PTEN Phosphohydrolase, Cell migration, Middle Aged, Prognosis, medicine.disease, Gene Knockdown Techniques, Cancer research, biology.protein, Female, Signal transduction, Proto-Oncogene Proteins c-akt |
| الوصف: | We integrated four gene expression profile data sets, namely two different pair-matched stage I lung adenocarcinoma data sets, secondary metastatic tumors vs benign tumors and lung tumor metastasizes to the brain, and we identified one kinase, T-LAK Cell-Originated Protein Kinase (TOPK), as a putative gene that promotes metastasis. To delineate the role of TOPK in lung cancer, we showed that overexpression of TOPK, but not a catalytically inactive form of TOPK, can enhance the migration and invasion of lung fibroblasts or cells with low TOPK expression. In addition, TOPK-induced cell migration was shown to be a PI3K/AKT-dependent event. TOPK concurrently promoted AKT phosphorylation at Ser(473) and decreased the phosphatase and tensin homolog (PTEN) levels, whereas TOPK knockdown had the reverse effects. LY294002, a PI3K inhibitor, did not inhibit the TOPK-induced decrease in PTEN, and co-expression of PTEN significantly reduced TOPK-induced AKT phosphorylation in a dose-dependent manner; these results indicate that the TOPK-mediated PTEN decrease has an upstream role in regulating PI3K/AKT-stimulated migration. Using immunohistochemical analysis of lung cancer tissue samples, we showed that a high TOPK expression level correlates strongly with reduced overall and disease-free survivals. Moreover, an inverse correlation between TOPK and PTEN expression was present and is consistent with the biochemical findings. Finally, a combination of high TOPK and low PTEN expression was inversely correlated with overall and disease-free survivals, independent of other pathologic staging factors. Our results suggest that TOPK is a potential therapeutic target in lung cancer that promotes cell migration by modulating a PI3K/PTEN/AKT-dependent signaling pathway; they also suggest that high TOPK expression, either alone or in combination with a low level of PTEN, may serve as a prognostic marker for lung cancer. |
| تدمد: | 1476-5594 0950-9232 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::24826e24512ab2d4bcdf962dd6408d27 https://doi.org/10.1038/onc.2011.419 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....24826e24512ab2d4bcdf962dd6408d27 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14765594 09509232 |
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