Background:The expression and function of ribosomal s6 protein kinase 4 (RSK4) in renal cell carcinoma (RCC) are unknown.Methods:Immunohistochemistry was used to detect the expression of RSK4 in RCC, and the relationship between RSK4 expression and clinicopathological features as well as prognosis of RCC patients was statistically analysed. Ectopic RSK4 expression in RCC cell lines was performed to determine its effect on cell cycle regulation, tumour invasiveness, and metastatic capability.Results:RSK4 was overexpressed in RCCs (P=0.003), compared with normal tissues, and the expression varied in different RCC subtypes (P=0.021), especially in two subtypes of papillary RCCs (P=0.001). RSK4 expression was positively correlated with high pT stage (P<0.001), high Fuhrman grade (P<0.001), lymph node involvement (P<0.001), and presence of distant metastasis (P=0.039), and could predict poor outcome in RCC patients. Molecular studies showed that overexpression of RSK4 could promote cell cycle progression and enhance the invasive and metastatic capability of RCC cell lines and vice versa.Conclusion:The expression pattern and molecular mechanisms of RSK4 in RCCs indicate that it could be a potential independent prognostic factor and serve as a new potential therapeutic target for RCC patients.
Bibliographical noteFunding Information:
We thank Professor Cajal (Department of Pathology, Vall d’Hebron University Hospital, Barcelona, Spain) and Professor Jian Zhang (Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi’an, China) for providing the human shRSK4 plasmids and the packaging plasmids. We are also grateful to the Department of Medical Records Xijing Hospital for excellent working conditions and for providing access to archival materials. The work is supported by the National Natural Science Foundation of China (No. 81001140 and No. 81272651).
- ribosomal s6 protein kinase 4; renal cell carcinoma; prognosis; invasion; metastasis