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Regulation of proliferation and invasion by the IGF signalling pathway in Epstein-Barr virus-positive gastric cancer

 Inhye Jeong  ;  Sun Kyoung Kang  ;  Woo Sun Kwon  ;  Hyun Jeong Kim  ;  Kyoo Hyun Kim  ;  Hyun Myong Kim  ;  Andre Lee  ;  Suk Kyeong Lee  ;  Thomas Bogenrieder  ;  Hyun Cheol Chung  ;  Sun Young Rha 
 Journal of Cellular and Molecular Medicine, Vol.22(12) : 5899-5908, 2018 
Journal Title
 Journal of Cellular and Molecular Medicine 
Issue Date
BI836845 ; IGF signalling pathway ; epstein-barr virus ; gastric cancer
Several carcinomas including gastric cancer have been reported to contain Epstein-Barr virus (EBV) infection. EBV-associated gastric cancer (EBVaGC) is classified as one of four molecular subtypes of gastric cancer by The Cancer Genome Atlas (TCGA) group with increased immune-related signatures. Identification of EBV-dependent pathways with significant biological roles is needed for EBVaGC. To compare the biological changes between AGS gastric epithelial cells and EBV-infected AGS (AGS-EBV) cells, proliferation assay, CCK-8 assay, invasion assay, cell cycle analysis, RT-PCR, Western blot and ELISA were performed. BI836845, a humanized insulin-like growth factor (IGF) ligand-neutralizing antibody, was used for IGF-related signalling pathway inhibition. AGS-EBV cells showed slower proliferating rate and higher sensitivity to BI836845 compared to AGS cells. Moreover, invasiveness of AGS-EBV was increased than that of AGS, and BI836845 treatment significantly decreased the invasiveness of AGS-EBV. Although no apoptosis was detected, entry into the S phase of the cell cycle was delayed in BI836845-treated AGS-EBV cells. In conclusion, AGS-EBV cells seem to modulate their proliferation and invasion through the IGF signalling pathway. Inhibition of the IGF signalling pathway therefore could be a potential therapeutic strategy for EBVaGC.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
라선영(Rha, Sun Young) ORCID logo https://orcid.org/0000-0002-2512-4531
정현철(Chung, Hyun Cheol) ORCID logo https://orcid.org/0000-0002-0920-9471
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