ArticleInternational journal of cancer2018
Alternative splice variants of DCLK1 mark cancer stem cells, promote self-renewal and drug-resistance, and can be targeted to inhibit tumorigenesis in kidney cancer.
Article in International journal of cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 71 citations in OpenAlex.
- Splicing-driven post-translational dysregulation: a new frontier for precision cancer medicine and immunotherapy.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Microtubule stiffening by the doublecortin-domain protein ZYG-8 contributes to mitotic spindle orientation during zygote division in Caenorhabditis elegans.PLoS genetics · 2026Article
- The advantages and challenges of sorafenib combination therapy: Drug resistance, toxicity and future directions (Review).Oncology letters · 2025Review
- A novel D-peptide modulates DCLK1 gelsolin interactions, reducing PDAC tumor growth.Scientific reports · 2025Article
- Hypoxic stimulation of DCLK1 transcription and alternative-promoter switching fuels tumor malignancy in clear cell renal cell carcinoma.Cell death & disease · 2025Article
- Balancing Regeneration and Resistance: Targeting DCLK1 to Mitigate Gastrointestinal Radiation Injury and Oncogenesis.Cancers · 2025Review
- Trends and hotspots in targeted therapy resistance research for renal cell carcinoma: a bibliometric and visualization analysis.Discover oncology · 2025Article
- FXYD5 regulates gastric cancer cell metastasis and drug resistance by EMT modulation.Cancer gene therapy · 2025Article
- 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
- Design and synthesis of doublecortin-like kinase 1 inhibitors and their bioactivity evaluation.Journal of enzyme inhibition and medicinal chemistry · 2024Article
- Targeting the PI3K/AKT/mTOR pathway offer a promising therapeutic strategy for cholangiocarcinoma patients with high doublecortin-like kinase 1 expression.Journal of cancer research and clinical oncology · 2024Article
- Article
- Colonic Tuft Cells: The Less-Recognized Therapeutic Targets in Inflammatory Bowel Disease and Colorectal Cancer.International journal of molecular sciences · 2024Review
- Kinome-wide siRNA screen identifies a DCLK2-TBK1 oncogenic signaling axis in clear cell renal cell carcinoma.Molecular cell · 2024Article
- Molecular subtyping and characterization of clear cell renal cell carcinoma by tumor differentiation trajectories.iScience · 2023Article
- Epigenetic Landscape and Therapeutic Implication of Gene Isoforms of Doublecortin-Like Kinase 1 for Cancer Stem Cells.International journal of molecular sciences · 2023Review
- Macrophage DCLK1 promotes atherosclerosis via binding to IKKβ and inducing inflammatory responses.EMBO molecular medicine · 2023Article
- Structure-Guided Prediction of the Functional Impact of DCLK1 Mutations on Tumorigenesis.Biomedicines · 2023Review
- Doublecortin-like kinase 1 is a therapeutic target in squamous cell carcinoma.Molecular carcinogenesis · 2023Article
- Article
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Authors and funding
16 authors at 7 institutions in 2 countries.
Funding
Abstract
Renal cell carcinoma (RCC) is a common and devastating disease characterized by a hypoxic microenvironment, epithelial-mesenchymal transition and potent resistance to therapy evidencing the presence of cancer stem cells (CSCs). Various CSC markers have been studied in RCC, but overall there is limited data on their role and most markers studied have been relatively nonspecific. Doublecortin-like kinase 1 (DCLK1) is a validated CSC marker in the gastrointestinal tract and evidence for an equivalent role in other cancers is accumulating. We used bioinformatics, immunohistochemistry, flow cytometry, spheroid self-renewal and chemoresistance assays in combination with overexpression and siRNA-knockdown to study the stem cell-supportive role of DCLK1 alternative splice variants (DCLK1 ASVs) in RCC. To target tumor cells expressing DCLK1 ASVs directly, we developed a novel monoclonal antibody (CBT-15) and delivered it systemically to RCC tumor xenografts. DCLK1 ASVs were overexpressed, enriched together with CSC markers and predictive of overall and recurrence-free survival in RCC patients. In vitro, DCLK1 ASVs were able to directly stimulate essential molecular and functional characteristics of renal CSCs including expression of aldehyde dehydrogenase, self-renewal and resistance to FDA-approved receptor tyrosine kinase and mTOR inhibitors, while targeted downregulation of DCLK1 reversed these characteristics. Finally, targeting DCLK1 ASV-positive cells with the novel CBT-15 monoclonal antibody blocked RCC tumorigenesis in vivo. These findings establish DCLK1 as a CSC marker with implications for therapy, disease progression and survival in RCC and demonstrate the therapeutic value of DCLK1-targeted monoclonal antibodies against renal CSCs.
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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.