ArticleCancer biology & therapy2025
RSK4 promotes the metastasis of clear cell renal cell carcinoma by activating RUNX1-mediated angiogenesis.
Article in Cancer biology & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- FAM65A, as a potential predictor of prognosis, promotes colorectal cancer progression via activating Ras/ERK/RSK signaling.iScience · 2026Article
- Expression of ribosomal S6 kinase 4 in bladder cancer and its correlation with clinicopathological features.Frontiers in oncology · 2026Article
- MX1 is a novel crucial prognostic and therapeutic target inducing chemoresistance in right-sided colon cancer: insights from machine learning-based multi-omics analysis.Human genomics · 2025Article
- P300 Promotes RUNX1 Transcription to Regulate Autophagy and Drive Corneal Neovascularization.Investigative ophthalmology & visual science · 2025Article
- Gastric metastasis of renal cell carcinoma: features, mechanisms, and insights from existing literature.Frontiers in cell and developmental biology · 2025Review
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Authors and funding
8 authors.
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Abstract
Ribosomal S6 protein kinase 4 (RSK4), a member of the serine‒threonine kinase family, plays a vital role in the Ras‒MAPK pathway. This kinase is responsible for managing several cellular activities, including cell growth, proliferation, survival, and mobility. In this study, we observed higher RSK4 protein expression in clear cell renal cell carcinoma (ccRCC) than in normal kidney tissue, and the overexpression of RSK4 might predict poor outcomes for ccRCC patients. Notably, renal cell carcinoma (RCC) is rich in blood vessels; therefore, this study aimed to explore the biological function of RSK4 in ccRCC progression and its specific regulatory mechanism. We analyzed changes in the expression of target genes through transcriptomic and proteomic assessments. We also conducted tube formation assays and VEGF ELISAs to understand the role of RSK4 in angiogenesis. Additionally, we evaluated the regulatory effect of RUNX1 on EPHA2 transcription using a luciferase reporter gene assay and observed that the effect of RUNX1 on activating EPHA2 transcription was negated after the binding site was mutated. Our findings suggested that RSK4 enhanced tube formation by stimulating VEGF secretion. Concurrently, in vivo experiments confirmed that RSK4 expedited RCC metastasis and angiogenesis. This evidence indicates that RSK4 may serve as a new prognostic marker and play a vital role in RCC metastasis.
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