Downregulation of SATB2 is critical for induction of epithelial-to-mesenchymal transition and invasion of NSCLC cells

Autor: Hakan Kucuksayan, Hakan Akca, Osman Nidai Ozes
Rok vydání: 2016
Předmět:
0301 basic medicine
Cancer Research
Lung Neoplasms
epithelial mesenchymal transition
cell transformation
NSCLC
fibroblast
Western blotting
lung tumor
transcription factor NANOG
gene silencing
Invasion
A549 cell line
Carcinoma
Non-Small-Cell Lung
transcription factor Sox2
morphology
genetics
Stemness
transcription factor
Hermes antigen
transforming growth factor beta
STAB2 protein
human
transcription factor Slug
biology
EMT
gene expression regulation
biological marker
cell invasion
unclassified drug
Gene Expression Regulation
Neoplastic
Cell Transformation
Neoplastic
priority journal
Oncology
Gene Knockdown Techniques
embryonic structures
Neoplastic Stem Cells
transcription factor Twist
down regulation
TGF-β
Pulmonary and Respiratory Medicine
Homeobox protein NANOG
octamer transcription factor 4
cancer stem cell
Epithelial-Mesenchymal Transition
Cell Adhesion Molecules
Neuronal
special at rich binding protein 2
Article
03 medical and health sciences
SATB2
nerve cell adhesion molecule
Gentamicin protection assay
Cell Line
Tumor
Humans
controlled study
Neoplasm Invasiveness
human
Epithelial–mesenchymal transition
protein expression
A549 cell
cell culture
non small cell lung cancer
human cell
CD44
tumor cell line
Transforming growth factor beta
tumor invasion
small interfering RNA
030104 developmental biology
TGF-ß
Cell culture
Immunology
Cancer cell
biology.protein
Cancer research
pathology
transcription factor ZEB1
metabolism
upregulation
Biomarkers
Zdroj: Lung Cancer. 98:122-129
ISSN: 0169-5002
DOI: 10.1016/j.lungcan.2016.05.032
Popis: 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. © 2016 Elsevier Ireland Ltd.
Databáze: OpenAIRE
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