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Cell migration and invasion were measured by wound-healing (e) and Transwell assays (f) in the presence or absence of LY294002. g Western blotting analysis of the expression of p-AKT, p-PI3K, total AKT and total PI3K. 6AGK stimulates the PI3K/AKT signalling pathway. a KEGG analysis was conducted to identify the pathways activated by AGK overexpression in RCC. b MTT assay, c colony formation assay and d flow cytometric analysis of the proliferation of the indicated RCC cells in the presence or absence of the PI3K inhibitor LY294002. Correction: Acylglycerol kinase promotes tumour growth and metastasis via activating the PI3K/AKT/GSK3 signalling pathway in renal cell carcinoma. [Extracted from the article]

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 reporter assays, immunofluorescence and in vivo experiments. Results: AGK expression is significantly elevated in RCC and closely related to the malignant development and poor prognosis in RCC patients. By in vitro and in vivo experiments, AGK was shown to enhance the proliferation of RCC cells by promoting the transition from the G1 phase to the S phase in the cell cycle and to enhance the migration and invasion by promoting epithelial-mesenchymal transition. By activating the PI3K/AKT/GSK3β signalling pathway in RCC, AGK can increase nuclear accumulation of β-catenin, which further upregulated TCF/LEF transcription factor activity. Conclusions: AGK promotes the progression of RCC via activating the PI3K/AKT/GSK3β signalling pathway and might be a potential target for the further research of RCC. [ABSTRACT FROM AUTHOR]

Eph receptors and the corresponding Eph receptor-interacting (ephrin) ligands jointly constitute a critical cell signaling network that has multiple functions. The tyrosine kinase EphA2, which belongs to the family of Eph receptors, is highly produced in tumor tissues, while found at relatively low levels in most normal adult tissues, indicating its potential application in cancer treatment. After 30 years of investigation, a large amount of data regarding EphA2 functions have been compiled. Meanwhile, several compounds targeting EphA2 have been evaluated and tested in clinical studies, albeit with limited clinical success. The present review briefly describes the contribution of EphA2-ephrin A1 signaling axis to carcinogenesis. In addition, the roles of EphA2 in resistance to molecular-targeted agents were examined. In particular, we focused on EphA2's potential as a target for cancer treatment to provide insights into the application of EphA2 targeting in anticancer strategies. Overall, EphA2 represents a potential target for treating malignant tumors. [ABSTRACT FROM AUTHOR]