Acylglycerol kinase promotes tumour growth and metastasis via activating the PI3K/AKT/GSK3β signalling pathway in renal cell carcinoma

作者：Qian Zhu, Ai-Lin Zhong, Hao Hu, Jing-Jing Zhao, De-Sheng Weng, Yan Tang, Qiu-Zhong Pan, Zi-Qi Zhou, Mengjia Song, Jie-Ying Yang, Junyi He, Yuan Liu, Min Li, Wan-Ming Hu, Chao-Pin Yang, Tong Xiang, Ming‐Yuan Chen, Gang Ma, Ling Guo, Jian‐Chuan Xia · 发表于：Journal of Hematology & Oncology · 年份：2020 · DOI：10.1186/s13045-019-0840-4 · 被引用次数：63 · 研究领域：PI3K/AKT/mTOR signaling in cancer、Cancer, Lipids, and Metabolism、Cancer, Stress, Anesthesia, and Immune Response

BACKGROUND: Clinically, the median survival in patients with metastatic renal cell carcinoma (RCC) was only 6-12 months and a 5-year survival rate of less than 20%. Therefore, an in-depth study of the molecular mechanisms involved in RCC is of great significance for improving the survival of patients with advanced RCC. Acylglycerol kinase (AGK) is a newly discovered lipid kinase that has been reported to be a potent oncogene that may be involved in the regulation of malignant progression in a variety of tumours. However, the expression and biological characteristics of the AGK gene in RCC remain unclear. METHODS: AGK expression was quantified by quantitative real-time PCR, Western blotting and immunohistochemistry in RCC cell lines and paired patient tissues. Kaplan-Meier method and Cox proportional hazards models were used to evaluate the prognostic value of AGK in human RCC tissue samples. Chi-squared test was performed to analyse the correlation between AGK expression and the clinicopathological features. Stable overexpression and knockdown of AGK in RCC cells was constructed with lentivirus. The oncogenic effects of AGK in human RCC progression were investigated using assays of colony formation, anchorage-independent growth, EdU assay, cell cycle analysis, wound-healing, trans-well analysis and xenograft tumour model. GSEA and KEGG analysis were conducted to detect the potential pathway of AGK involved in RCC. These results were further confirmed using the luciferase repo...