Snail regulated by PKC/GSK-3β pathway is crucial for EGF-induced epithelial-mesenchymal transition (EMT) of cancer cells
| العنوان: | Snail regulated by PKC/GSK-3β pathway is crucial for EGF-induced epithelial-mesenchymal transition (EMT) of cancer cells |
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| المؤلفون: | Shaohui Cai, Ge Zhang, Rui Fang, Hong-Sheng Wang, Hai-xing Song, Hao Wang, Xiao-Hui Chen, Hao Liu, Jun Du, Dan-yang Chen, Zong-Cai Liu |
| المصدر: | Cell and Tissue Research. 358:491-502 |
| بيانات النشر: | Springer Science and Business Media LLC, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Epithelial-Mesenchymal Transition, Histology, Transcription, Genetic, Snail, Pathology and Forensic Medicine, Glycogen Synthase Kinase 3, Cell Movement, Epidermal growth factor, Cell Line, Tumor, Neoplasms, biology.animal, Humans, Neoplasm Invasiveness, Epithelial–mesenchymal transition, Protein kinase B, Protein Kinase C, Protein kinase C, PI3K/AKT/mTOR pathway, Cell Nucleus, Glycogen Synthase Kinase 3 beta, Epidermal Growth Factor, biology, Protein Stability, Cell Biology, Up-Regulation, Cell biology, Protein Transport, Cancer cell, Snail Family Transcription Factors, Signal transduction, Signal Transduction, Transcription Factors |
| الوصف: | Cancer metastasis is considered a major challenge in cancer therapy. Recently, epidermal growth factor (EGF)/epidermal growth factor receptor (EGFR) signaling has been shown to induce epithelial-mesenchymal transition (EMT) and thereby to promote cancer metastasis. However, the underlying mechanism has not been fully elucidated. We demonstrate that EGF can induce EMT in human prostate and lung cancer cells and thus promote invasion and migration. EGF-induced EMT has been characterized by the cells acquiring mesenchymal spindle-like morphology and increasing their expression of N-cadherin and fibronectin, with a concomitant decrease of E-cadherin. Both protein and mRNA expression of transcription factor Snail rapidly increases after EGF treatment. The knockdown of Snail significantly attenuates EGF-induced EMT, suggesting that Snail is crucial for this process. To determine the way that Snail is accumulated, we demonstrate (1) that EGF promotes the stability of Snail via inhibiting the activity of glycogen synthase kinase 3 beta (GSK-3β), (2) that protein kinase C (PKC) rather than the phosphatidylinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway is responsible for GSK-3β inhibition and (3) that GSK-3β inhibition promotes the transcription of Snail. Taken together, these results reveal that the PKC/GSK-3β signaling pathway controls both the stability and transcription of Snail, which is crucial for EMT induced by EGF in PC-3 and A549 cells. Our study suggests a novel signaling pathway for Snail regulation and provides a better understanding of growth-factor-induced tumor EMT and metastasis. |
| تدمد: | 1432-0878 0302-766X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::512aa953aa5ae320df28b21b7c8496e2 https://doi.org/10.1007/s00441-014-1953-2 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....512aa953aa5ae320df28b21b7c8496e2 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 14320878 0302766X |
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