Insulin-like growth factor-I induces epithelial to mesenchymal transition via GSK-3β and ZEB2 in the BGC-823 gastric cancer cell line.

Heming Li,Yunpeng Liu,Zhitu Zhu,Yanju Ma,Lei Zhao,Ling Xu,Xiujuan Qu

doi:10.3892/ol.2014.2687

Abstract

Metastasis is the most common cause of mortality in patients with gastric cancer. Epithelial-to-mesenchymal transition (EMT), which may be stimulated by insulin-like growth factor-I (IGF-I) is involved in the metastasis of numerous tumors; however, the molecular mechanism by which IGF-I may induce tumor cell EMT remains to be elucidated in gastric cancer. The present study aimed to investigate the induction of EMT in BGC-823 gastric cancer cells. It was identified that IGF-I induced EMT by upregulating the levels of ZEB2 transcription factor, and this was dependent on the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway in these cells. In addition, glycogen synthase kinase 3β (GSK-3β), an intracellular downstream effector of PI3K/Akt, sustained the epithelial phenotype by repressing ZEB2 expression and the subsequent inhibition of EMT induced by IGF-I, suggesting the involvement of a potential PI3K/Akt-GSK-3β-ZEB2 signaling pathway in IGF-I-induced EMT in gastric cancer BGC-823 cells. Overall, the results of the present study suggest that IGF-I induced EMT by the activation of a PI3K/Akt-GSK-3β-ZEB2 signaling pathway in gastric cancer BGC-823 cells. Therefore, this study may provide more useful information regarding the mechanism of gastric cancer metastasis.

Highlights

Gastric cancer is one of the most common types of cancer worldwide and the predominant cause of cancer‐related mortality in Asian countries annually [1,2]
These data demonstrated that insulin‐like growth factor‐I (IGF‐I) could upregulate ZEB2 and induce Epithelial-to-mesenchymal transition (EMT) in BGC‐823 gastric cancer cells
Transforming growth factor‐β‐mediated ZEB2 expression has been shown to be involved in the process of EMT and enhancement of invasive ability in several types of epithelial tumor cells [27,28]; whether IGF‐I can upregulate the expression of ZEB2 is yet to be elucidated

Summary

Introduction

Gastric cancer is one of the most common types of cancer worldwide and the predominant cause of cancer‐related mortality in Asian countries annually [1,2]. The majority of patients are diagnosed with advanced disease, in China [3]. Advanced gastric cancer is characterized by a highly invasive Investigations on the molecular mechanisms of tumor metastasis will provide potential molecular targets and biomarkers for the development of effective therapies for gastric cancer

Methods

Results

Conclusion