GLS1 promotes proliferation in hepatocellular carcinoma cells via AKT/GSK3β/CyclinD1 pathway

• Published in: Experimental cell research 2019-08, Vol.381 (1), p.1-9
• Main Authors: Xi, Jianbo, Sun, Yaocheng, Zhang, Meiting, Fa, Zhenzhong, Wan, Yanya, Min, Zhenyu, Xu, Hong, Xu, Chengkai, Tang, Jianjun
• Format: Article
• Language: English
• Subjects: AKT/GSK3β/CyclinD1 pathway; Animals; Benzophenanthridines - pharmacology; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Cell Line, Tumor; Cell Proliferation; Cyclin D1 - metabolism; Disease Progression; Drug Delivery Systems; Female; Glutaminase - antagonists & inhibitors; Glutaminase - genetics; Glutaminase - metabolism; Glutaminase 1 (GLS1); Glycogen Synthase Kinase 3 beta - metabolism; Hepatocellular carcinoma (HCC); Humans; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Male; Mice; Mice, Nude; Middle Aged; Oncogenes; Proto-Oncogene Proteins c-akt - metabolism; Retrospective Studies; Signal Transduction; Up-Regulation
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2019.04.005

Glutamine metabolism is an important metabolic pathway for cancer cell survival, and there is a critical connection between tumor growth and glutamine metabolism. However, the role of GLS1 in hepatocellular carcinoma (HCC) progression remains to be elucidated. In this study, we reported that GLS1 expression was significantly increased in HCC tissues and correlated with serum AFP, tumor differentiation, lymphatic metastasis, TNM stage, and poorer patient outcome. We further showed that GLS1 promoted colony formation and cell proliferation of HCC cells. Furthermore, our data showed that GLS1 inhibitor compound 968 inhibited the proliferation of HCC cells in a dose-dependent manner. Importantly, we found that GLS1 overexpression increased p-AKT, p-GSK3β and cyclinD1 expression, and had no influence on total AKT and GSK3β protein level, indicating that GLS1 was involved in AKT/GSK3β/CyclinD1 pathway. It is suggested that GLS1 promotes proliferation in HCC cells probably via AKT/GSK3β/CyclinD1 pathway and may be a potential target for anti-hepatocellular carcinoma cancer. •GLS1 expression is highly dysregulated in HCC tissues and associated with malignant clinical parameters.•GLS1 promotes colony formation and cell proliferation of HCC cells.•GLS1 inhibitor compound 968 inhibited the proliferation of HCC cells in a dose-dependent manner.•GLS1 was involved in AKT/GSK3β/CyclinD1 pathway in HCC cells.