ArticleGastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association2020
Phosphoproteomic analysis identifies CLK1 as a novel therapeutic target in gastric cancer.
Article in Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 54 citations in OpenAlex.
- Deconvoluting the multi-faceted roles of alternative splicing events in cancer: From underlying mechanisms to innovative therapeutics.Acta pharmaceutica Sinica. B · 2026Review
- CLK1 Promotes Myeloid-Derived Suppressor Cell Trafficking and Reprograms the Tumor Microenvironment by Activating Hippo/YAP Signaling in Colorectal Cancer.Cancer immunology research · 2026Article
- Review
- Genome-wide CRISPR-Cas9 screening identifies CLK1 inhibition as a strategy to restore PARP inhibitor sensitivity via ERCC1 isoform switching.Protein & cell · 2026Article
- Decoding SR protein regulation: kinases, phosphatases, and therapeutic targeting strategies.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- YTHDC1 orchestrates oncogenic splicing via the CLK1-SRSF1 splicing machinery to regulate castration-resistant prostate cancer progression.Molecular and cellular biochemistry · 2025Article
- Pharmacological CLK inhibition disrupts SR protein function and RNA splicing blocking cell growth and migration in TNBC.Breast cancer research : BCR · 2025Article
- Controlled by disorder: Phosphorylation modulates SRSF1 domain availability for spliceosome assembly.Protein science : a publication of the Protein Society · 2025Article
- Targeting RNA splicing modulation: new perspectives for anticancer strategy?Journal of experimental & clinical cancer research : CR · 2025Review
- Targeting CLK2 and serine/arginine-rich splicing factors inhibits multiple myeloma through downregulating RAE1 by nonsense-mediated mRNA decay mechanism.Cancer science · 2025Article
- Regulatory interplay between SR proteins governsRNA (New York, N.Y.) · 2024Article
- Context-aware single-cell multiomics approach identifies cell-type-specific lung cancer susceptibility genes.Nature communications · 2024Article
- Multi-omics characterization of esophageal squamous cell carcinoma identifies molecular subtypes and therapeutic targets.JCI insight · 2024Article
- Differential Expression of SRY-Related HMG-Box Transcription Factor 2, Oligodendrocyte Lineage Transcription Factor 2, and Zinc Finger E-Box Binding Homeobox 1 in Serum-Derived Extracellular Vesicles: Implications for Mithramycin Sensitivity and Targeted Therapy in High-Grade Glioma.ACS pharmacology & translational science · 2024Article
- Development of 5-hydroxybenzothiophene derivatives as multi-kinase inhibitors with potential anti-cancer activity.Future medicinal chemistry · 2024Article
- Machine learning-based selection of immune cell markers in osteosarcoma: prognostic determination and validation of CLK1 in disease progression.Frontiers in immunology · 2024Article
- Development and validation of a prognostic model based on RNA binding proteins in patients with esophageal cancer.Journal of thoracic disease · 2023Article
- Context-aware single-cell multiome approach identified cell-type specific lung cancer susceptibility genes.bioRxiv : the preprint server for biology · 2023Article
- CLASRP oncogene as a novel target for colorectal cancer.Functional & integrative genomics · 2023Article
- A Comprehensive Pan-Cancer Analysis Identifies CEP55 as a Potential Oncogene and Novel Therapeutic Target.Diagnostics (Basel, Switzerland) · 2023Article
Corrections and comments
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Authors and funding
22 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPhosphorylation is an important regulatory mechanism of protein activity in cells. Studies in various cancers have reported perturbations in kinases resulting in aberrant phosphorylation of oncoproteins and tumor suppressor proteins.
methodsIn this study, we carried out quantitative phosphoproteomic analysis of gastric cancer tissues and corresponding xenograft samples. Using these data, we employed bioinformatics analysis to identify aberrant signaling pathways. We further performed molecular inhibition and silencing of the upstream regulatory kinase in gastric cancer cell lines and validated its effect on cellular phenotype. Through an ex vivo technology utilizing patient tumor and blood sample, we sought to understand the therapeutic potential of the kinase by recreating the tumor microenvironment.
resultsUsing mass spectrometry-based high-throughput analysis, we identified 1,344 phosphosites and 848 phosphoproteins, including differential phosphorylation of 177 proteins (fold change cut-off ≥ 1.5). Our data showed that a subset of differentially phosphorylated proteins belonged to splicing machinery. Pathway analysis highlighted Cdc2-like kinase (CLK1) as upstream kinase. Inhibition of CLK1 using TG003 and CLK1 siRNA resulted in a decreased cell viability, proliferation, invasion and migration as well as modulation in the phosphorylation of SRSF2. Ex vivo experiments which utilizes patient's own tumor and blood to recreate the tumor microenvironment validated the use of CLK1 as a potential target for gastric cancer treatment.
conclusionsOur data indicates that CLK1 plays a crucial role in the regulation of splicing process in gastric cancer and that CLK1 can act as a novel therapeutic target in gastric cancer.
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