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https://hdl.handle.net/11499/8928
Title: | The crosstalk between p38 and Akt signaling pathways orchestrates EMT by regulating SATB2 expression in NSCLC cells | Authors: | Küçüksayan, Hakan Akça, Hakan |
Keywords: | Akt epithelial–mesenchymal transition non-small-cell lung cancer p38 SATB2 mitogen activated protein kinase p38 phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase protein kinase B transcription factor transcription factor SATB2 unclassified drug matrix attachment region binding protein PTEN protein, human SATB2 protein, human Akt signaling Article AT rich sequence controlled study enzyme activation epigenetics epithelial mesenchymal transition gene silencing lung metastasis lung non-small cell carcinoma cell line molecular dynamics molecular interaction non small cell lung cancer priority journal protein expression upregulation biosynthesis gene expression regulation human lung tumor MAPK signaling metabolism pathology physiology signal transduction tumor cell line Western blotting Blotting, Western Carcinoma, Non-Small-Cell Lung Cell Line, Tumor Epithelial-Mesenchymal Transition Gene Expression Regulation, Neoplastic Gene Knockdown Techniques Humans Lung Neoplasms MAP Kinase Signaling System Matrix Attachment Region Binding Proteins Proto-Oncogene Proteins c-akt PTEN Phosphohydrolase Receptor Cross-Talk Signal Transduction Transcription Factors |
Publisher: | SAGE Publications Ltd | Abstract: | Epithelial–mesenchymal transition is a crucial event for metastasis and could be mediated by several pathways such as phosphoinositide 3-kinase/Akt, mitogen-activated protein kinases, as well as many epigenetic regulators. Special AT-rich sequence-binding protein 2 is an epigenetic regulator involved in epithelial–mesenchymal transition and osteoblastic differentiation. It has been reported that the crosstalk between several pathways is responsible for the regulation of epithelial–mesenchymal transition in cancer cells. However, crosstalks between p38 and Akt pathways involved in epithelial–mesenchymal transition are still unknown. We recently reported that there is a crosstalk between p38 and Akt pathways in non-small-cell lung carcinoma cells, and this crosstalk is associated with E-cadherin and special AT-rich sequence-binding protein 2 expressions. Therefore, we aimed to determine whether this crosstalk has a mediator role in the regulation of epithelial–mesenchymal transition in non-small-cell lung carcinoma. Our results showed that inhibition of p38 leads to the disruption of this crosstalk via decreased expression of phosphatase and tensin homolog (PTEN) and subsequently increased activation of Akt in non-small-cell lung carcinoma cells. Then, we found that p38 inhibition upregulated special AT-rich sequence-binding protein 2 expression and reversed epithelial–mesenchymal transition in non-small-cell lung carcinoma cells. Furthermore, special AT-rich sequence-binding protein 2 knockdown abolished the effect of p38 inhibition on epithelial–mesenchymal transition in non-small-cell lung carcinoma cells. In conclusion, our results strongly indicate that the crosstalk between p38 and Akt pathways can determine special AT-rich sequence-binding protein 2 expression and epithelial character of non-small-cell lung carcinoma cells, and special AT-rich sequence-binding protein 2 is a critical epigenetic regulator for epithelial–mesenchymal transition mediated by p38 pathway in non-small-cell lung carcinoma. Our findings will contribute to illuminate the molecular mechanisms of the epithelial–mesenchymal transition process that has a critical significance for lung cancer metastasis. © 2017, © The Author(s) 2017. | URI: | https://hdl.handle.net/11499/8928 https://doi.org/10.1177/1010428317706212 |
ISSN: | 1010-4283 |
Appears in Collections: | PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection Tıp Fakültesi Koleksiyonu WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection |
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