ArticleJournal of translational medicine2021
ELK4 promotes the development of gastric cancer by inducing M2 polarization of macrophages through regulation of the KDM5A-PJA2-KSR1 axis.
Article in Journal of translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- tRNA-derived fragments: mechanism of gene regulation and clinical application in lung cancer.Cellular oncology (Dordrecht, Netherlands) · 2024Pooled it
- Lung cancer cell-derived exosomal EHF drives M2 macrophage polarization via transcriptional activation of RNF41 to promote tumor progression.Regenerative therapy · 2026Article
- Role of histone modifications in gastric cancer (Review).International journal of oncology · 2026Review
- The JMJD family histone demethylases: structure, mechanism of action, diseases and therapeutic targets.Molecular biomedicine · 2026Review
- Advances in Tumor-Derived Exosomal Non-Coding RNAs Regulating M2 Macrophage Polarization: Molecular Mechanisms and Signaling Pathway.Cancer medicine · 2025Review
- LncRNA SNHG16 Drives PD-L1-Mediated Immune Escape in Colorectal Cancer through Regulating miR-324-3p/ELK4 Signaling.Biochemical genetics · 2025Article
- Aberrant PJA2-CHRM3 signaling creates a therapeutic vulnerability in gastric tumor.British journal of cancer · 2025Article
- TRIM32 promotes tumor immune evasion and impedes Anti-PD-1 treatment by inducing immunosuppressive macrophages in gastric cancer.Journal of translational medicine · 2025Article
- Type 1 interferon signature and allograft inflammatory factor-1 contribute to refractoriness to TNF inhibition in ankylosing spondylitis.Nature communications · 2025Article
- ELK4 transcription promotes MSI2-mediated progression of non-small cell lung cancer through the TGF-β/SMAD3 pathway.The Kaohsiung journal of medical sciences · 2025Article
- PJA2 Suppresses Colorectal Cancer Progression by Controlling HDAC2 Degradation and Stability.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Integrative single-cell and spatial transcriptomics uncover ELK4-mediated mechanisms inFrontiers in immunology · 2025Article
- ZC3H13 promotes autophagy in bladder cancer through m6A methylation modification of PJA2 and ubiquitination of KSR1.Human cell · 2024Article
- ELK4 targets CHMP6 to inhibit ferroptosis and enhance malignant properties of skin cutaneous melanoma cells.Archives of dermatological research · 2024Article
- TWEAK/Fn14 signalling driven super-enhancer reprogramming promotes pro-metastatic metabolic rewiring in triple-negative breast cancer.Nature communications · 2024Article
- Hypoxia increases the biogenesis of IGF2BP3-bound circular RNAs.Molecular biology reports · 2024Article
- Identifying possible hub genes and biological mechanisms shared between bladder cancer and inflammatory bowel disease using machine learning and integrated bioinformatics.Journal of cancer research and clinical oncology · 2023Article
- The ALKBH5/SOX4 axis promotes liver cancer stem cell properties via activating the SHH signaling pathway.Journal of cancer research and clinical oncology · 2023Article
- ELK4 Promotes Cell Cycle Progression and Stem Cell-like Characteristics in HPV-associated Cervical Cancer by Regulating the FBXO22/PTEN AxisBalkan medical journal · 2023Article
- Hsa_circ_0119412 Contributes to Development of Retinoblastoma by Targeting miR-186-5p/ELK4 Axis.Molecular biotechnology · 2023Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWe tried to elaborate the molecular mechanism of ETS-like transcription factor 4 (ELK4) affecting gastric cancer (GC) progression through M2 polarization of macrophages mediated by lysine-specific demethylase 5A (KDM5A)-Praja2 (PJA2)-kinase suppressor of ras 1 (KSR1) axis.
methodsGC expression dataset was obtained from GEO database, and the downstream regulatory mechanism of ELK4 was predicted. Tumor-associated macrophages (TAMs) were isolated from GC tissues. The interaction among ELK4, KDM5A, PJA2 and KSR1 was analyzed by dual luciferase reporter gene, ChIP and Co-IP assays. The stability of KSR1 protein was detected by cycloheximide (CHX) treatment. After TAMs were co-cultured with HGC-27 cells, HGC-27 cell biological processes were assessed through gain- and loss-of function assays. Tumorigenicity was detected by tumorigenicity test in nude mice.
resultsIn GC and TAMs, ELK4, KDM5A and KSR1 were highly expressed, while PJA2 was lowly expressed. M2 polarization of macrophages promoted the development of GC. ELK4 activated KDM5A by transcription and promoted macrophage M2 polarization. KDM5A inhibited the expression of PJA2 by removing H3K4me3 of PJA2 promoter, which promoted M2 polarization of macrophages. PJA2 reduced KSR1 by ubiquitination. ELK4 promoted the proliferative, migrative and invasive potentials of GC cells as well as the growth of GC xenografts by regulating KSR1.
conclusionELK4 may reduce the PJA2-dependent inhibition of KSR1 by transcriptional activation of KDM5A to promote M2 polarization of macrophages, thus promoting the development of GC.
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