ArticleScientific reports2015
Epigenetic changes and alternate promoter usage by human colon cancers for expressing DCLK1-isoforms: Clinical Implications.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 72 citations in OpenAlex.
- DCLK1 regulates stemness and IL-6/STAT3-dependent metastatic niche formation in chemoresistant ovarian cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- miR-136-5p Preferentially Suppresses Cancer Stem-like Cells in Pancreatic Cancer.International journal of molecular sciences · 2026Article
- Tumor necrosis factor promotes doublecortin-like kinase 1 expression and cellular reprogramming in intestinal epithelial cells leading to neoplastic transformation.Cell communication and signaling : CCS · 2025Article
- Hypoxic stimulation of DCLK1 transcription and alternative-promoter switching fuels tumor malignancy in clear cell renal cell carcinoma.Cell death & disease · 2025Article
- DCLK1 isoform (DCLK1-S) as a critical player in promoting inflammation, tissue remodeling, and EMT in mouse models of colitis.PLoS pathogens · 2025Article
- Osteocalcin induces phosphorylation of FOXO1 in human beta-cells and restores insulin expression under hyperglycemic conditions.Research square · 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
- IL-13Rα2 Is Involved in Resistance to Doxorubicin and Survival of Osteosarcoma Patients.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Isolating Circulating Cancer Stem Cells (CCSCs) from Human Whole Blood.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Targeting doublecortin-like kinase 1 reveals a novel strategy to circumvent chemoresistance and metastasis in ovarian cancer.Cancer letters · 2023Article
- Epigenetic Landscape and Therapeutic Implication of Gene Isoforms of Doublecortin-Like Kinase 1 for Cancer Stem Cells.International journal of molecular sciences · 2023Review
- Proteomic investigation of neural stem cell to oligodendrocyte precursor cell differentiation reveals phosphorylation-dependent Dclk1 processing.Cellular and molecular life sciences : CMLS · 2023Article
- Structure-Guided Prediction of the Functional Impact of DCLK1 Mutations on Tumorigenesis.Biomedicines · 2023Review
- Review
- Targeting Doublecortin-Like Kinase 1 (DCLK1)-Regulated SARS-CoV-2 Pathogenesis in COVID-19.Journal of virology · 2022Article
- Oncogenic functions and clinical significances of DCLK1 isoforms in colorectal cancer: a systematic review and meta-analysis.Cancer cell international · 2022Review
- Functional assessment of miR‑1291 in colon cancer cells.International journal of oncology · 2022Article
- DCLK1 autoinhibition and activation in tumorigenesis.Innovation (Cambridge (Mass.)) · 2022Article
- DCLK1 promotes colorectal cancer stemness and aggressiveness via the XRCC5/COX2 axis.Theranostics · 2022Article
- Pleiotropic effects of DCLK1 in cancer and cancer stem cells.Frontiers in molecular biosciences · 2022Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
DCLK1 specifically marks colon/pancreatic cancers in mice, and is expressed by human colon adenocarcinomas (hCRCs). Down-regulation of DCLK1 results in loss of cancer-stem-cells (CSCs), and inhibits spheroidal/xenograft growths from hCRC-cells. The 5'-promoter of DCLK1-gene is reportedly hypermethylated in hCRCs, resulting in loss of expression of DCLK1-transcripts, originating from 5'(α)-promoter (termed DCLK1-L, in here). However, in mouse colon-tumors, 5'-promoter of DCLK1-gene remains unchanged, and DCLK1-L, originating from 5'(α)-promoter, is expressed. We hypothesized that elevated levels of DCLK1-protein in hCRC-cells, may be transcribed/translated from an alternate-promoter. Several in silico and molecular biology approaches were used to test our hypothesis. We report for the first time that majority of hCRCs express short-transcripts of DCLK1 (termed DCLK1-S, in here) from an alternate β-promoter in IntronV of the gene, while normal-colons mainly express DCLK1-L from 5'(α)-promoter. We additionally report an important role of β-catenin and TCF4/LEF binding-sites for activating (α)-promoter, while activated NF-κBp65 (bound to NF-κB-cis-element), activates (β)-promoter in cancer-cells. DCLK1-S expression was examined in a cohort of 92 CRC patients; high-expressors had significantly worse overall-survival compared to low-expressors. Our novel findings' regarding usage of alternate (β)-promoter by hCRCs, suggests that DCLK1-S may represent an important target for preventing/inhibiting colon-cancers, and for eliminating colon-CSCs.
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Registered trials
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.