The mechanism of epithelial-mesenchymal transition induced by TGF-β1 in neuroblastoma cells

Shao,Jing-Bo; Gao,Zhi-Mei; Huang,Wen-Yan; Lu,Zhi-Bao

doi:10.3892/ijo.2017.3954

The mechanism of epithelial-mesenchymal transition induced by TGF-β1 in neuroblastoma cells

Authors:
- Jing-Bo Shao
- Zhi-Mei Gao
- Wen-Yan Huang
- Zhi-Bao Lu
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Affiliations: Department of Hematology/Oncology, Shanghai Children's Hospital, Shanghai Jiaotong University, Shanghai 200040, P.R. China, Department of Central Laboratory, Shanghai Children's Hospital, Shanghai Jiaotong University, Shanghai 200040, P.R. China, Department of Nephrology, Shanghai Children's Hospital, Shanghai Jiaotong University, Shanghai 200040, P.R. China, Department of General Surgery, Shanghai Children's Hospital, Shanghai Jiaotong University, Shanghai 200040, P.R. China
Published online on: April 5, 2017 https://doi.org/10.3892/ijo.2017.3954
Pages: 1623-1633
Copyright: © Shao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Neuroblastoma is the second most common extracranial malignant solid tumor that occurs in childhood, and metastasis is one of the major causes of death in neuroblastoma patients. The epithelial-mesenchymal transition (EMT) is an important mechanism for both the initiation of tumor invasion and subsequent metastasis. Therefore, this study investigated the mechanism by which transforming growth factor (TGF)-β1 induces EMT in human neuroblastoma cells. Using quantitative RT-qPCR and western blot analyses, we found that the mRNA and protein expression levels of E-cadherin were significantly decreased, whereas that of α-SMA was significantly increased after neuroblastoma cells were treated with different concentrations of TGF-β1. A scratch test and Transwell migration assay revealed that cell migration significantly and directly correlated with the concentration of TGF-β1 indicating that TGF-β1 induced EMT in neuroblastoma cells and led to their migration. Inhibiting Smad2/3 expression did not affect the expression of the key molecules involved in EMT. Further investigation found that the expression of the glioblastoma transcription factor (Gli) significantly increased in TGF-β1-stimulated neuroblastoma cells undergoing EMT, accordingly, interfering with Gli1/2 expression inhibited TGF-β1-induced EMT in neuroblastoma cells. GANT61, which is a targeted inhibitor of Gli1 and Gli2, decreased cell viability and promoted cell apoptosis. Thus, TGF-β1 induced EMT in neuroblastoma cells to increase their migration. Specifically, EMT induced by TGF-β1 in neuroblastoma cells did not depend on the Smad signaling pathway, and the transcription factor Gli participated in TGF-β1-induced EMT independent of Smad signaling.

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