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Downregulation of SATB2 is critical for induction of epithelial-to-mesenchymal transition and invasion of NSCLC cells       
Yazarlar
Dr. Öğr. Üyesi Hakan KÜÇÜKSAYAN
Kastamonu Üniversitesi, Türkiye
Osman Nidai Özeş
Türkiye
Hakan Akça
Türkiye
Özet
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-β-induced EMT and invasion of NSCLC cells, and found that SATB2 is downregulated in A549 cells and TGF-β can induce EMT in these cells, however, TGF-β 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-β-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.
Anahtar Kelimeler
EMT | Invasion | NSCLC | SATB2 | Stemness | TGF-β
Makale Türü Özgün Makale
Makale Alt Türü SSCI, AHCI, SCI, SCI-Exp dergilerinde yayımlanan tam makale
Dergi Adı LUNG CANCER
Dergi ISSN 0169-5002
Dergi Tarandığı Indeksler SCI
Makale Dili Türkçe
Basım Tarihi 08-2016
Cilt No 98
Sayı 8
Sayfalar 122 / 129
Doi Numarası 10.1016/j.lungcan.2016.05.032
Makale Linki http://dx.doi.org/10.1016/j.lungcan.2016.05.032