Article Abstract

Effects of GLS1 on the epithelial-mesenchymal transition of hepatocellular carcinoma in vitro and in vivo

Authors: Yajuan Cao, Binghua Li, Xianbiao Shi, Hongyan Wu, Chen Yan, Ouyang Luo, Decai Yu, Yitao Ding


Background: To evaluate the effects of GLS1 on epithelial-mesenchymal transition (EMT) of hepatocellular carcinoma (HCC) in vivo and in vitro.
Methods: HCC cells HCCLM3 overexpressing GLS1 were constructed by lentiviral vector PCDH-CMVMCS- EF1-Puro GLS1. HCCLM3 cells with GLS1 knockdown were constructed by sgRNA-GLS. Nude mice were subcutaneously implanted with HCCLM3-LV-GLS1 cells (Group A), HCCLM3-sgRNA-GLS1 cells (Group B) and HCCLM3 cells (Group C) respectively.
Results: The proliferation, migration and invasion of HCCLM3-LV-GLS1 cells increased, but those of HCCLM3-sgRNA-GLS1 cells decreased. The expression of epithelial marker E-cadherin decreased in HCCLM3-LV-GLS1 cells, but those of mesenchymal marker vimentin and transcription factor ZEB1 increased. The expressions of matrix metalloproteinase 2 (MMP2) and MMP9 proteins in HCCLM3-LVGLS1 cells increased with extended time. Group B had significantly lower tumor formation rate and smaller tumor volume. Tumor formation was unaffected in Group A which had a similar tumor volume to that of Group C. With decreasing GLS1 expression, the expression of E-cadherin was up-regulated but that of vimentin was down-regulated. The expressions of Slug and ZEB1 in EMT-related signaling pathways were up-regulated. Group A had a higher MMP2 expression than that of Group B.
Conclusions: HCC may be effectively treated by inhibiting glutamine metabolism, and GLS1 is a potentially new metabolic target