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The crosstalk between p38 and Akt signaling pathways orchestrates EMT by regulating SATB2 expression in NSCLC cells

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dc.contributor.author Küçüksayan, Hakan
dc.contributor.author Akça, Hakan
dc.date.accessioned 2019-08-16T12:57:11Z
dc.date.available 2019-08-16T12:57:11Z
dc.date.issued 2017
dc.identifier.issn 10104283 (ISSN)
dc.identifier.uri http://acikerisim.pau.edu.tr:8080/xmlui/handle/11499/8928
dc.description.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.
dc.language.iso English
dc.publisher SAGE Publications Ltd
dc.relation.isversionof 10.1177/1010428317706212
dc.rights info:eu-repo/semantics/openAccess
dc.subject Akt
dc.subject epithelial–mesenchymal transition
dc.subject non-small-cell lung cancer
dc.subject p38
dc.subject SATB2
dc.subject mitogen activated protein kinase p38
dc.subject phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase
dc.subject protein kinase B
dc.subject transcription factor
dc.subject transcription factor SATB2
dc.subject unclassified drug
dc.subject matrix attachment region binding protein
dc.subject PTEN protein, human
dc.subject SATB2 protein, human
dc.subject Akt signaling
dc.subject Article
dc.subject AT rich sequence
dc.subject controlled study
dc.subject enzyme activation
dc.subject epigenetics
dc.subject epithelial mesenchymal transition
dc.subject gene silencing
dc.subject lung metastasis
dc.subject lung non-small cell carcinoma cell line
dc.subject molecular dynamics
dc.subject molecular interaction
dc.subject non small cell lung cancer
dc.subject priority journal
dc.subject protein expression
dc.subject upregulation
dc.subject biosynthesis
dc.subject gene expression regulation
dc.subject human
dc.subject lung tumor
dc.subject MAPK signaling
dc.subject metabolism
dc.subject pathology
dc.subject physiology
dc.subject signal transduction
dc.subject tumor cell line
dc.subject Western blotting
dc.subject Blotting, Western
dc.subject Carcinoma, Non-Small-Cell Lung
dc.subject Cell Line, Tumor
dc.subject Epithelial-Mesenchymal Transition
dc.subject Gene Expression Regulation, Neoplastic
dc.subject Gene Knockdown Techniques
dc.subject Humans
dc.subject Lung Neoplasms
dc.subject MAP Kinase Signaling System
dc.subject Matrix Attachment Region Binding Proteins
dc.subject Proto-Oncogene Proteins c-akt
dc.subject PTEN Phosphohydrolase
dc.subject Receptor Cross-Talk
dc.subject Signal Transduction
dc.subject Transcription Factors
dc.title The crosstalk between p38 and Akt signaling pathways orchestrates EMT by regulating SATB2 expression in NSCLC cells
dc.type Article
dc.relation.journal Tumor Biology
dc.identifier.volume 39
dc.identifier.issue 9
dc.relation.publicationCategory Uluslararası Hakemli Dergi
dc.identifier.index Scopus
dc.identifier.index PubMed


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