ArticleClinical and translational medicine2022
Targeting DCLK1 overcomes 5-fluorouracil resistance in colorectal cancer through inhibiting CCAR1/β-catenin pathway-mediated cancer stemness.
Article in Clinical and translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 25 citations in OpenAlex.
- DCLK1 mediates airway epithelial barrier disruption through NF-κB activation in severe asthma.Molecular medicine (Cambridge, Mass.) · 2026Article
- Doublecortin-like kinase 1 promotes fibroblast activation and fibrotic progression through Smad3 binding in idiopathic pulmonary fibrosis.Journal of biomedical science · 2026Article
- FNDC4 Drives Metastasis and Immune Evasion in Pancreatic Cancer.Cancer research · 2026Article
- Ccar1 prevents β-catenin nuclear translocation to sustain ground-state pluripotency in mouse ESCs under R2i.Biochemistry and biophysics reports · 2025Article
- Serine/Threonine Kinase 33 as a Novel Target of Bufalin in Treatment of Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Doublecortin-like kinase 1, regulated by STIP1 homology and U-box containing protein 1 or Sp1 transcription factor, affects the malignant behaviors and drug sensitivity in adriamycin-resistant breast cancer cells.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Hypoxic stimulation of DCLK1 transcription and alternative-promoter switching fuels tumor malignancy in clear cell renal cell carcinoma.Cell death & disease · 2025Article
- Extrachromosomal circular DNA and their roles in cancer progression.Genes & diseases · 2025Review
- Clinical significance of "S" isoform of DCLK1 in different gastric cancer subtypes using newly produced monoclonal antibody.Cancer biomarkers : section A of Disease markers · 2025Article
- Phytochemicals in Drug Discovery-A Confluence of Tradition and Innovation.International journal of molecular sciences · 2024Review
- Colonic Tuft Cells: The Less-Recognized Therapeutic Targets in Inflammatory Bowel Disease and Colorectal Cancer.International journal of molecular sciences · 2024Review
- Intestinal Tuft Cells: Morphology, Function, and Implications for Human Health.Annual review of physiology · 2024Review
- Crosstalk between colorectal CSCs and immune cells in tumorigenesis, and strategies for targeting colorectal CSCs.Experimental hematology & oncology · 2024Review
- The Combination of 5-FU and Resveratrol Can Suppress the Growth of Glioblastoma Cells Through Downregulation of TRPM2 and β-Catenin.Journal of molecular neuroscience : MN · 2024Article
- NDR1/FBXO11 promotes phosphorylation-mediated ubiquitination of β-catenin to suppress metastasis in prostate cancer.International journal of biological sciences · 2024Article
- Long noncoding RNA NONHSAT160169.1 promotes resistance via hsa-let-7c-3p/SOX2 axis in gastric cancer.Scientific reports · 2023Article
- Epigenetic Landscape and Therapeutic Implication of Gene Isoforms of Doublecortin-Like Kinase 1 for Cancer Stem Cells.International journal of molecular sciences · 2023Review
- Article
- PRAME Is a Novel Target of Tumor-Intrinsic Gas6/Axl Activation and Promotes Cancer Cell Invasion in Hepatocellular Carcinoma.Cancers · 2023Article
- Deciphering treatment resistance in metastatic colorectal cancer: roles of drug transports, EGFR mutations, and HGF/c-MET signaling.Frontiers in pharmacology · 2023Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTo date, 5-fluorouracil-based chemotherapy is very important for locally advanced or metastatic colorectal cancer (CRC). However, chemotherapy resistance results in tumor recurrence and metastasis, which is a major obstacle for treatment of CRC.
methodsIn the current research, we establish 5-fluorouracil resistant cell lines and explore the potential targets associated with 5-fluorouracil resistance in CRC. Moreover, we perform clinical specimen research, in vitro and in vivo experiments and molecular mechanism research, to reveal the biological effects and the mechanism of DCLK1 promoting 5-fluorouracil resistance, and to clarify the potential clinical value of DCLK1 as a target of 5-fluorouracil resistance in CRC.
resultsWe discover that doublecortin-like kinase 1 (DCLK1), a cancer stem cell maker, is correlated with 5-fluorouracil resistance, and functionally promotes cancer stemness and 5-fluorouracil resistance in CRC. Mechanistically, we elucidate that DCLK1 interacts with cell cycle and apoptosis regulator 1 (CCAR1) through the C-terminal domain, and phosphorylates CCAR1 at the Ser343 site, which is essential for CCAR1 stabilisation. Moreover, we find that DCLK1 positively regulates β-catenin signalling via CCAR1, which is responsible for maintaining cancer stemness. Subsequently, we prove that blocking β-catenin inhibits DCLK1-mediated 5-fluorouracil resistance in CRC cells. Importantly, we demonstrate that DCLK1 inhibitor could block CCAR1/β-catenin pathway-mediated cancer stemness and consequently suppresses 5-fluorouracil resistant CRC cells in vitro and in vivo.
conclusionsCollectively, our findings reveal that DCLK1 promotes 5-fluorouracil resistance in CRC by CCAR1/β-catenin pathway-mediated cancer stemness, and suggest that targeting DCLK1 might be a promising method to eliminate cancer stem cells for overcoming 5-fluorouracil resistance in CRC.
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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 Socratic graph.