ArticleThe Journal of clinical investigation2020
Ribosomal S6 protein kinase 4 promotes radioresistance in esophageal squamous cell carcinoma.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 74 citations in OpenAlex.
- A patent perspective of RSK inhibitors to treat cancer (2020-present).Expert opinion on therapeutic patents · 2026Review
- Rational Design of Novel Thiazole-Clubbed Pyrimidine-Linked Hydrazone Conjugates as Promising RSK4 Inhibitors for Esophageal Squamous Cell Carcinoma: Molecular Dynamics Simulations and In Vitro Evaluation.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Review
- Restoring the tumour mechanophenotype of vocal fold cancer reverts its malignant properties.Nature materials · 2026Article
- Macrophage efferocytosis mediated by the TP63-RAC2 pathway promotes immunosuppressive remodeling in esophageal cancer.Cell reports. Medicine · 2026Article
- Expression of ribosomal S6 kinase 4 in bladder cancer and its correlation with clinicopathological features.Frontiers in oncology · 2026Article
- O-GlcNAcylation stabilizes RSK4 by antagonizing GSK3β-mediated phosphorylation to enhance radioresistance in esophageal squamous cell carcinoma.International journal of biological sciences · 2026Article
- SNORA58 Facilitates Radioresistance via Suppressing JNK1-Mediated Ferroptosis in Esophageal Squamous Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- RiSKs in Computational Modeling of Isoform-Selective RSK Inhibitors.Journal of chemical information and modeling · 2025Review
- KLF5 promotes esophageal squamous cell carcinoma radioresistance by targeting the Keap1-Nrf2 pathway.Discover oncology · 2025Article
- Modification-specific Proteomic Analysis Reveals Cysteine S-Palmitoylation Involved in Esophageal Cancer Cell Radiation.ACS omega · 2025Article
- ΔNp63α promotes radioresistance in esophageal squamous cell carcinoma through the PLEC-KEAP1-NRF2 feedback loop.Cell death & disease · 2024Article
- Ribosomal S6 kinase (RSK) plays a critical role in DNA damage response via the phosphorylation of histone lysine demethylase KDM4B.Breast cancer research : BCR · 2024Article
- Ribosome biogenesis and ribosomal proteins in cancer stem cells: a new therapeutic prospect.Molecular biology reports · 2024Review
- The TDP-43/TP63 Positive Feedback Circuit Promotes Esophageal Squamous Cell Carcinoma Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Review
- Article
- Updating mRNA variants of the human RSK4 gene and their expression in different stressed situations.Heliyon · 2024Article
- Neuropilin-2 acts a critical determinant for epithelial-to-mesenchymal transition and aggressive behaviors of human head and neck cancer.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Expression of RSK4 protein in non-small cell lung cancer tissues, adjacent tissues and its correlation with clinicopathological features.American journal of translational research · 2024Article
Corrections and comments
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Authors and funding
26 authors at 8 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancers and is highly resistant to current treatments. ESCC harbors a subpopulation of cells exhibiting cancer stem-like cell (CSC) properties that contribute to therapeutic resistance including radioresistance, but the molecular mechanisms in ESCC CSCs are currently unknown. Here, we report that ribosomal S6 protein kinase 4 (RSK4) plays a pivotal role in promoting CSC properties and radioresistance in ESCC. RSK4 was highly expressed in ESCC CSCs and associated with radioresistance and poor survival in patients with ESCC. RSK4 was found to be a direct downstream transcriptional target of ΔNp63α, the main p63 isoform, which is frequently amplified in ESCC. RSK4 activated the β-catenin signaling pathway through direct phosphorylation of GSK-3β at Ser9. Pharmacologic inhibition of RSK4 effectively reduced CSC properties and improved radiosensitivity in both nude mouse and patient-derived xenograft models. Collectively, our results strongly suggest that the ΔNp63α/RSK4/GSK-3β axis plays a key role in driving CSC properties and radioresistance in ESCC, indicating that RSK4 is a promising therapeutic target for ESCC treatment.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.