ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2023
ELK4 Promotes Colorectal Cancer Progression by Activating the Neoangiogenic Factor LRG1 in a Noncanonical SP1/3-Dependent Manner.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- Revealing the multiple faces of LRG1: gene expression, structure, function, and therapeutic potential.Journal of advanced research · 2026Review
- CellSNVReg: a multidimensional resource for SNV-mediated regulatory perturbations in single-cell and spatial omics.Nucleic acids research · 2026Article
- LncRNA SNHG16 Drives PD-L1-Mediated Immune Escape in Colorectal Cancer through Regulating miR-324-3p/ELK4 Signaling.Biochemical genetics · 2025Article
- HMGB1 downregulates DDX3 to activate the MAPK pathway, promoting the progression of colorectal cancer.Cancer gene therapy · 2025Article
- The critical role of LRG1 in pathological fibrosis.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Gut-derivedmSystems · 2025Article
- YAP/TEAD4/SP1-induced VISTA expression as a tumor cell-intrinsic mechanism of immunosuppression in colorectal cancer.Cell death and differentiation · 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
- ELK4 Promotes Vasculogenic Mimicry in Oral Squamous Cell Carcinoma via DrivingOncology research · 2025Article
- Integrative single-cell and spatial transcriptomics uncover ELK4-mediated mechanisms inFrontiers in immunology · 2025Article
- Mesangial Cells in Diabetic Kidney Disease: From Mechanisms to Therapeutic Implications.International journal of biological sciences · 2025Review
- Natural products modulating MAPK for CRC treatment: a promising strategy.Frontiers in pharmacology · 2025Review
- Tumor-infiltrating immune cell signature score reveals prognostic biomarkers and therapeutic targets for colorectal cancer.Frontiers in immunology · 2025Article
- Article
- The RNA helicase DDX21 activates YAP to promote tumorigenesis and is transcriptionally upregulated by β-catenin in colorectal cancer.Oncogene · 2024Article
- ELK4 targets CHMP6 to inhibit ferroptosis and enhance malignant properties of skin cutaneous melanoma cells.Archives of dermatological research · 2024Article
- The disruptive role of LRG1 on the vasculature and perivascular microenvironment.Frontiers in cardiovascular medicine · 2024Review
- ELK4 Promotes Colorectal Cancer Progression by Activating the Neoangiogenic Factor LRG1 in a Noncanonical SP1/3-Dependent Manner.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Although the MAPK/MEK/ERK pathway is prevalently activated in colorectal cancer (CRC), MEK/ERK inhibitors show limited efficiency in clinic. As a downstream target of MAPK, ELK4 is thought to work primarily by forming a complex with SRF. Whether ELK4 can serve as a potential therapeutic target is unclear and the transcriptional regulatory mechanism has not been systemically analyzed. Here, it is shown that ELK4 promotes CRC tumorigenesis. Integrated genomics- and proteomics-based approaches identified SP1 and SP3, instead of SRF, as cooperative functional partners of ELK4 at genome-wide level in CRC. Serum-induced phosphorylation of ELK4 by MAPKs facilitated its interaction with SP1/SP3. The pathological neoangiogenic factor LRG1 is identified as a direct target of the ELK4-SP1/SP3 complex. Furthermore, targeting the ELK4-SP1/SP3 complex by combination treatment with MEK/ERK inhibitor and the relatively specific SP1 inhibitor mithramycin A (MMA) elicited a synergistic antitumor effect on CRC. Clinically, ELK4 is a marker of poor prognosis in CRC. A 9-gene prognostic model based on the ELK4-SP1/3 complex-regulated gene set showed robust prognostic accuracy. The results demonstrate that ELK4 cooperates with SP1 and SP3 to transcriptionally regulate LRG1 to promote CRC tumorigenesis in an SRF-independent manner, identifying the ELK4-SP1/SP3 complex as a potential target for rational combination therapy.
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