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Title: | Downregulation of SATB2 is critical for induction of epithelial-to-mesenchymal transition and invasion of NSCLC cells | Authors: | Küçüksayan, Hakan Ozes, O.N. Akça, Hakan |
Keywords: | EMT Invasion NSCLC SATB2 Stemness TGF-ß Hermes antigen octamer transcription factor 4 small interfering RNA special at rich binding protein 2 transcription factor transcription factor NANOG transcription factor Slug transcription factor Sox2 transcription factor Twist transcription factor ZEB1 transforming growth factor beta unclassified drug biological marker nerve cell adhesion molecule STAB2 protein, human A549 cell line Article cell culture cell invasion controlled study down regulation epithelial mesenchymal transition fibroblast gene silencing human human cell morphology non small cell lung cancer priority journal protein expression upregulation Western blotting cancer stem cell cell transformation gene expression regulation genetics lung tumor metabolism pathology tumor cell line tumor invasion Biomarkers Carcinoma, Non-Small-Cell Lung Cell Adhesion Molecules, Neuronal Cell Line, Tumor Cell Transformation, Neoplastic Epithelial-Mesenchymal Transition Gene Expression Regulation, Neoplastic Gene Knockdown Techniques Gene Silencing Humans Lung Neoplasms Neoplasm Invasiveness Neoplastic Stem Cells |
Publisher: | Elsevier Ireland Ltd | Abstract: | Objectives: The epithelial-to-mesenchymal transition (EMT) is considered as a key step in invasion of cancer cells. There are several regulator proteins responsible for induction of EMT, but underlying mechanisms are still unclear. SATB2 is an epigenetic regulator involved in osteoblastic differentiation. The role of SATB2 in EMT and invasion of NSCLC cells is unknown. Therefore, we aimed to explain roles of SATB2 with underlying molecular mechanisms in EMT and invasion of NSCLC cells. Materials and methods: We used A549 and NCI-H1650 cells as a model to evaluate the effects of SATB2 in EMT and invasion of NSCLC cells. Cell culture, western blot analysis, siRNA-mediated gene knockdown, and invasion assay were performed in this study. Results and conclusion: In this study, we investigated the regulatory role of SATB2 expression in TGF-ß-induced EMT and invasion of NSCLC cells, and found that SATB2 is downregulated in A549 cells and TGF-ß can induce EMT in these cells, however, TGF-ß can not induce EMT in SATB2 expressing cells such as H1650, PC3, II-18, Hcc78 and Hcc193. Our results demonstrated that SATB2 knockdown is sufficient to induce generation of fibroblast-like morphology, EMT and invasion of NSCLC cells by upregulating the expressions of Slug, Twist and Zeb1. Moreover, SATB2 knockdown promotes TGF-ß-induced EMT and invasion in NSCLC cells. These results strongly suggest that SATB2 prevents induction of EMT by suppressing expression of EMT-inducing transcription factors in NSCLC cells. Furthermore, SATB2 could inhibit tumour initiation by suppressing stemness marker genes such as CD44, Nanog, Oct-4A and Sox-2. Consequently, our results clearly indicate that SATB2 plays pivotal role in EMT, invasion and stemness of NSCLC cells. © 2016 Elsevier Ireland Ltd. | URI: | https://hdl.handle.net/11499/9495 https://doi.org/10.1016/j.lungcan.2016.05.032 |
ISSN: | 0169-5002 |
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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