Affinage

DCLK1

Serine/threonine-protein kinase DCLK1 · UniProt O15075

Length
740 aa
Mass
82.2 kDa
Annotated
2026-04-28
100 papers in source corpus 26 papers cited in narrative 26 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DCLK1 is a bifunctional protein that couples microtubule regulation with serine/threonine kinase signaling across neuronal development, epithelial homeostasis, and inflammatory responses. Its N-terminal doublecortin-like domain directly polymerizes and bundles microtubules independently of kinase activity, labels dendritic microtubules to guide KIF1-dependent vesicle trafficking, and is required for dendrite development (PMID:11124993, PMID:26758546). The C-terminal kinase domain is held in autoinhibition by an autoinhibitory domain that competitively blocks the ATP-binding site until Ca²⁺-bound HPCAL1 releases it; once active, DCLK1 phosphorylates MAP7D1 (promoting axon elongation), IKKβ S177/181 (activating NF-κB-driven inflammation and atherosclerosis), XRCC5/Ku80 (activating COX-2/PGE₂), and CCAR1 S343 (stabilizing β-catenin signaling and cancer stemness) (PMID:34977835, PMID:27503845, PMID:36896602, PMID:35910805, PMID:35522902). In cancer, DCLK1 sustains EMT and immune evasion by repressing tumor-suppressor miRNAs (let-7a, miR-200, miR-145), upregulating CXCL1-mediated MDSC recruitment, and is driven by a cancer-specific short isoform transcribed from an alternative β-promoter activated by NF-κBp65 (PMID:19445940, PMID:24040120, PMID:36309200, PMID:26447334).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2000 High

    Establishing DCLK1 as a bifunctional protein resolved whether the doublecortin-like domain and kinase domain operate independently: the microtubule polymerization/bundling activity was shown to be kinase-independent, defining DCLK1 as both a MAP and a kinase.

    Evidence In vitro tubulin polymerization with purified DCAMKL1, kinase-dead mutagenesis, and live-cell imaging in cell lines

    PMID:11124993

    Open questions at the time
    • Identity of physiological kinase substrates unknown
    • Regulation of kinase activation not addressed
    • In vivo function not tested
  2. 2004 High

    Discovery that the C-terminal domain functions as an autoinhibitory element (removal causing ~10-fold kinase activation) established a regulatory paradigm for DCLK1 kinase control, but the structural basis and activating signal remained unknown.

    Evidence In vitro kinase assay with CaMK substrates and truncation mutagenesis of short DCLK splice variants

    PMID:14741399

    Open questions at the time
    • Structural mechanism of autoinhibition unresolved
    • Physiological signal that relieves autoinhibition unknown
    • Whether autoinhibition operates in vivo not demonstrated
  3. 2009 High

    Linking DCLK1 to tumor-suppressor miRNA regulation answered how a kinase/MAP protein controls cancer stemness: DCLK1 negatively regulates let-7a biogenesis, and its knockdown induces let-7a and suppresses c-Myc, establishing a non-canonical oncogenic function.

    Evidence siRNA knockdown in CRC cell lines and xenografts; let-7a luciferase reporter; FACS sorting of DCLK1⁺ cells

    PMID:19445940

    Open questions at the time
    • Mechanism by which DCLK1 represses let-7a biogenesis (direct or indirect) unresolved
    • Whether kinase activity is required for miRNA regulation unknown
  4. 2011 High

    Extension to miR-200a, miR-144, and EMT transcription factor networks broadened DCLK1's oncogenic role beyond let-7a, demonstrating that DCLK1 controls multiple miRNA axes converging on EMT, KRAS, and Notch signaling in pancreatic cancer.

    Evidence siRNA knockdown in pancreatic cancer cells; miRNA qRT-PCR; immunoblot; IHC in mouse model

    PMID:21285251 PMID:24040120

    Open questions at the time
    • Direct versus indirect mechanism of miRNA repression still unclear
    • No kinase-dead rescue to test kinase dependence
  5. 2013 High

    Genetic epistasis in mice revealed an unexpected skeletal function: Dclk1 represses osteoblast differentiation by antagonizing Runx2, and Dclk1 loss rescues cleidocranial dysplasia in Runx2⁺/⁻ mice, establishing DCLK1 as a physiological brake on bone formation.

    Evidence Dclk1 knockout mice; genetic epistasis with Runx2⁺/⁻; shRNA screen; bone formation analysis

    PMID:23918955

    Open questions at the time
    • Molecular mechanism linking DCLK1 to Runx2 inhibition (direct phosphorylation vs. intermediate) not identified
    • Cell-type specificity of effect in bone not resolved
  6. 2015 Medium

    Identification of alternative promoter usage (α-promoter for long isoform in normal epithelium; β-promoter for short isoform in cancer driven by NF-κBp65) resolved the paradox of DCLK1 as both a normal cell marker and cancer protein, attributing oncogenic functions to the short isoform.

    Evidence Promoter cloning and luciferase reporter assays; qRT-PCR across patient cohort

    PMID:26447334

    Open questions at the time
    • Functional differences between long and short isoforms not fully dissected biochemically
    • Promoter switch mechanism in tumorigenesis not defined
    • Single-lab finding
  7. 2016 High

    A systematic kinesin screen established that DCLK1-decorated microtubules serve as a dendritic transport code recognized by KIF1 motors, explaining how DCLK1 directs dense-core vesicle trafficking into dendrites and supports dendrite morphogenesis.

    Evidence Screen of 45 kinesins; live-cell DCV trafficking assay; KD/KO in hippocampal neurons

    PMID:26758546

    Open questions at the time
    • How DCLK1 labeling is restricted to dendritic microtubules unknown
    • Whether kinase activity modulates the MAP-based trafficking role not tested
  8. 2016 High

    Identification of MAP7D1 as a direct DCLK1 kinase substrate (phosphorylated at S315) provided the first defined neuronal substrate linking DCLK1 kinase activity specifically to axon elongation rather than radial migration.

    Evidence Phosphoproteomic substrate identification; in vitro kinase assay; phosphomimetic S315E rescue of Dclk1 KD axon defect in cortical neurons

    PMID:27503845

    Open questions at the time
    • Additional neuronal substrates likely exist but are unidentified
    • Whether MAP7D1 phosphorylation affects microtubule dynamics directly not tested
  9. 2018 High

    Intestinal epithelial Dclk1 knockout revealed that tuft-cell DCLK1 is required for injury-induced COX-2 expression and PGE₂ production, establishing a paracrine epithelial repair mechanism where PGE₂ rescues proliferative defects in Dclk1-deficient organoids.

    Evidence Villin-Cre;Dclk1-flox intestinal KO mice; colonic organoid culture with PGE₂ rescue

    PMID:30478383

    Open questions at the time
    • Whether DCLK1 kinase activity is required for COX-2 induction or whether the MAP domain contributes not distinguished
    • Upstream signal activating DCLK1 in tuft cells upon injury unknown
  10. 2019 High

    Epigenetic control of DCLK1 was established when KDM3A was shown to bind the DCLK1 promoter and demethylate H3K9me1/2, directly activating DCLK1 transcription in pancreatic cancer and linking chromatin remodeling to DCLK1-driven stemness and invasion.

    Evidence ChIP for KDM3A at DCLK1 promoter; KDM3A shRNA/overexpression; RNA-seq; orthotopic tumor model

    PMID:31442435

    Open questions at the time
    • Whether other histone marks or chromatin remodelers regulate DCLK1 not explored
    • Relationship between KDM3A regulation and isoform-specific promoter usage not addressed
  11. 2020 High

    Development of DCLK1-IN-1 and a chemical-genetic toolkit (resistance mutation G532A, kinase-dead mutants) formally demonstrated that kinase activity drives cancer cell migration and growth, and phosphoproteomics revealed regulation of RNA processing pathways and CDK11 as a candidate substrate.

    Evidence Selective inhibitor DCLK1-IN-1; engineered DCLK1-dependent cells; resistance mutations; phosphoproteomics

    PMID:32755567

    Open questions at the time
    • CDK11 as substrate not validated by in vitro phosphorylation
    • RNA processing pathway mechanism downstream of DCLK1 kinase not elucidated
  12. 2021 High

    Crystal structure of the autoinhibited DCLK1 kinase domain revealed that the AID competitively blocks the ATP-binding site; Ca²⁺-dependent HPCAL1 binding to the AID releases autoinhibition, finally identifying the physiological activation signal for DCLK1 kinase and explaining how cancer-associated AID mutations constitutively activate kinase activity.

    Evidence X-ray crystallography of autoinhibited kinase; HPCAL1–AID direct binding assay; Ca²⁺ dependence; cancer mutation analysis

    PMID:34977835

    Open questions at the time
    • Whether HPCAL1 is the sole activator in all tissue contexts unknown
    • Structural basis of HPCAL1–AID interaction not resolved at atomic level
  13. 2021 High

    Co-crystal structures of DCLK1 with DCLK1-IN-1 showed the inhibitor induces a drastic ATP-site conformational change without disrupting MAP function, formally separating kinase and MAP activities at the structural level.

    Evidence X-ray crystallography of DCLK1–inhibitor complexes; MAP function assay under inhibitor treatment

    PMID:34545159

    Open questions at the time
    • Whether kinase-independent MAP functions contribute to cancer phenotypes not resolved
    • Selectivity profile of DCLK1-IN-1 across the kinome not fully established
  14. 2022 High

    Identification of XRCC5/Ku80 as a direct DCLK1 phosphorylation target that transcriptionally activates COX-2 provided a molecular mechanism linking DCLK1 kinase activity to PGE₂-driven pro-inflammatory tumor microenvironment remodeling in CRC.

    Evidence Proteomics-based partner identification; Co-IP; in vitro kinase assay; COX-2 reporter; CRC mouse models

    PMID:35910805

    Open questions at the time
    • Specific phosphorylation site(s) on XRCC5 not mapped
    • Relationship to XRCC5's known DNA repair function not explored
  15. 2022 High

    DCLK1 was shown to drive immune evasion by upregulating CXCL1, which recruits MDSCs via CXCR2 and suppresses CD8⁺ T cell infiltration; CXCL1 overexpression rescued tumor growth in DCLK1-KO cells, establishing a specific immune-evasion axis.

    Evidence CRISPR KO tumor transplantation in immune-competent mice; flow cytometry; MDSC–T cell co-culture; CXCL1 rescue

    PMID:36309200

    Open questions at the time
    • Mechanism by which DCLK1 upregulates CXCL1 (kinase-dependent or not) undefined
    • Whether DCLK1-mediated immune evasion operates in non-CRC cancers not tested
  16. 2023 High

    Direct phosphorylation of IKKβ at S177/181 by DCLK1 in macrophages established DCLK1 as a bona fide upstream activator of canonical NF-κB signaling; macrophage-specific DCLK1 deletion attenuated atherosclerosis, defining a cell-type-specific inflammatory kinase function outside epithelial tissues.

    Evidence Co-IP/LC-MS/MS; in vitro phosphorylation; macrophage-specific KO in ApoE⁻/⁻ mice; RNA-seq

    PMID:36896602

    Open questions at the time
    • Whether DCLK1 phosphorylates IKKβ in epithelial cells not tested
    • Upstream signal activating DCLK1 in macrophages not identified
  17. 2023 High

    Extension to obesity-induced cardiomyopathy showed macrophage DCLK1 mediates RIP2/TAK1 phosphorylation upon palmitate challenge, linking DCLK1 to metabolic inflammation beyond atherosclerosis and demonstrating that cardiomyocyte DCLK1 is dispensable for this phenotype.

    Evidence Macrophage-specific and cardiomyocyte-specific DCLK1 KO mice on HFD; immunoblot for RIP2/TAK1 phosphorylation; RNA-seq

    PMID:37443105

    Open questions at the time
    • Whether DCLK1 directly phosphorylates RIP2 and/or TAK1 not demonstrated by in vitro kinase assay
    • Generalizability to other metabolic inflammatory conditions unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How DCLK1's kinase versus MAP activities are coordinately regulated in vivo, and whether Ca²⁺/HPCAL1 activation operates in non-neuronal tissues (e.g., tuft cells, macrophages), remain central unresolved questions.
  • No in vivo demonstration of HPCAL1-dependent DCLK1 activation in any tissue
  • Full substrate repertoire undefined—most substrates identified in single studies
  • How isoform-specific expression (DCLK1-L vs. DCLK1-S) differentially engages MAP and kinase functions in normal versus cancer contexts is mechanistically unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 8 GO:0008092 cytoskeletal protein binding 3
Localization
GO:0005829 cytosol 2 GO:0005856 cytoskeleton 2
Pathway
R-HSA-1643685 Disease 7 R-HSA-162582 Signal Transduction 5 R-HSA-168256 Immune System 4 R-HSA-1266738 Developmental Biology 3
Partners
ATMCCAR1HPCAL1IKBKBKIF1AKRASMAP7D1XRCC5

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 DCLK1 (DCAMKL1) protein associates with microtubules, stimulates polymerization of purified tubulin, and induces formation of aster-like microtubule structures and microtubule bundling in cell lines; its kinase domain is functional (phosphorylates myelin basic protein and itself), but kinase activity is dispensable for microtubule polymerization activity. In vitro microtubule polymerization assay with purified DCAMKL1; transfection/overexpression with time-lapse imaging; in vitro kinase assay; kinase-dead mutagenesis The Journal of neuroscience High 11124993
2004 Two short splice variants of DCLK (DCLK-short-A and -B) both phosphorylate autocamtide and syntide (CaMK-specific substrates); removal of the distinct C-terminal ends causes a ~10-fold increase in kinase activity, indicating the C-termini function as autoinhibitory domains. In vitro kinase assay with CaMK substrates; truncation mutagenesis of C-terminal domains Brain research. Molecular brain research High 14741399
2009 siRNA-mediated knockdown of DCAMKL-1 in colorectal cancer cells and xenografts results in tumor growth arrest, upregulation of pri-let-7a miRNA, decreased luciferase activity from a let-7a reporter, and decreased c-Myc expression, establishing DCAMKL-1 as a negative regulator of let-7a miRNA biogenesis. siRNA knockdown in HCT116/SW480 cells; xenograft model; luciferase reporter assay for let-7a; FACS-sorted DCAMKL-1+ cells analyzed for pri-let-7a Gastroenterology High 19445940
2011 siRNA knockdown of DCAMKL-1 in human pancreatic cancer cells induces miR-200a (an EMT inhibitor), downregulates ZEB1, ZEB2, Snail, Slug, Twist, and reduces c-Myc and KRAS through a let-7a-dependent mechanism, and reduces Notch-1 through a miR-144-dependent mechanism. siRNA knockdown; miRNA qRT-PCR; immunoblot; colocalization IHC in mouse model Cancer research High 21285251
2013 DCAMKL1 represses osteoblast differentiation by antagonizing Runx2 (the master osteoblast transcription factor); Dcamkl1-null mice display elevated bone mass secondary to increased bone formation, and the cleidocranial dysplasia phenotype of Runx2+/- mice is reversed by introduction of a Dcamkl1-null allele. shRNA forward genetic screen; targeted disruption of Dcamkl1 (knockout mouse); epistasis with Runx2+/- mice; molecular experiments The Journal of experimental medicine High 23918955
2013 DCLK1 knockdown in pancreatic cancer xenografts upregulates miR-145, leading to decreased OCT4, SOX2, NANOG, KLF4, KRAS, and RREB1; increases let-7a, decreasing LIN28B; and increases miR-200, decreasing VEGFR1, VEGFR2, and EMT transcription factors ZEB1, ZEB2, SNAIL, SLUG. Luciferase reporter assays confirmed post-transcriptional regulation. PLGA-nanoparticle siRNA knockdown in xenografts; miRNA/mRNA qRT-PCR; luciferase reporter assay PloS one High 24040120
2016 DCLK1 labels a subset of dendritic microtubules and is required for KIF1 (kinesin-3)-dependent dense-core vesicle trafficking into dendrites and for dendrite development in hippocampal neurons; systematic kinesin screen identified DCLK1-labeled microtubules as a dendritic transport cue. Systematic screen of 45 kinesin family members; live-cell imaging; KD/KO in hippocampal neurons; DCV trafficking assay The EMBO journal High 26758546
2016 DCLK1 phosphorylates MAP7D1 at Serine 315 to promote axon elongation in cortical neurons; knockdown of MAP7D1 impairs callosal axon elongation but not radial migration, and a phosphomimetic MAP7D1 S315E mutant rescues axon elongation defects in Dclk1 knockdown neurons. Proteomic identification of substrate; in vitro kinase assay; shRNA knockdown in cortical neurons; rescue with phosphomimetic mutant (S315E) Developmental neurobiology High 27503845
2018 DCLK1 induces NF-κBp65 expression through the PI3K/Akt/Sp1 axis and activates NF-κBp65 through PI3K/Akt/IκBα during EMT in colorectal cancer cells; silencing DCLK1 inhibits CRC invasion and metastasis in vivo. siRNA knockdown; immunoblot; pathway inhibitor experiments; in vivo metastasis model International journal of cancer Medium 29277893
2018 Dclk1 expression in intestinal tuft cells is required for inflammation-induced Cox2 expression and prostaglandin E2 (PGE2) production; PGE2 rescues proliferative defects in Dclk1-deficient colonic organoids, linking Dclk1 to epithelial repair via a PGE2-dependent paracrine mechanism. Villin-Cre;Dclk1flox/flox (intestinal epithelial knockout mice); colonic organoid culture; PGE2 rescue experiments; qPCR and immunostaining Cell death and differentiation High 30478383
2019 KDM3A (histone demethylase that removes H3K9me1/2) binds to the DCLK1 promoter and positively regulates DCLK1 expression in pancreatic cancer; knockdown of KDM3A reduces DCLK1 levels and impairs invasion, migration, and spheroid formation. ChIP assay for KDM3A binding at DCLK1 promoter; KDM3A shRNA knockdown; KDM3A overexpression; RNA-seq; orthotopic tumor model Gastroenterology High 31442435
2016 Dclk1 interaction with ATM is critical for ATM activation and DNA damage response following radiation injury; Dclk1 deletion reduces ATM-mediated pro-survival signaling and impairs intestinal crypt restitution. VillinCre;Dclk1flox/flox mice; total body irradiation; co-immunoprecipitation (DCLK1–ATM interaction); analysis of ATM phosphorylation and COX2 activation Scientific reports Medium 27876863
2021 The DCLK1 C-terminal autoinhibitory domain (AID) blocks the ATP-binding site competitively; neuronal calcium sensor HPCAL1 binds directly to the AID in a Ca2+-dependent manner, releasing autoinhibition and activating kinase activity; cancer-associated mutations in the AID disrupt autoinhibition to upregulate kinase activity. Crystal structure of DCLK1 kinase in autoinhibited state; direct binding assay (HPCAL1–AID); Ca2+-dependence assays; biochemical analysis of AID mutations Innovation High 34977835
2021 Crystal structures of DCLK1 kinase domain in complex with inhibitor DCLK1-IN-1 reveal that the compound induces a drastic conformational change of the ATP binding site; DCLK1-IN-1 binds DCLK1 long isoforms but does not prevent DCLK1's MAP (microtubule-associated protein) function, separating kinase and MAP activities. X-ray crystallography of DCLK1 kinase domain–inhibitor complex; structure-activity relationship analysis; MAP function assay Communications biology High 34545159
2020 DCLK1 kinase activity is required for DCLK1-dependent cancer cell migration and growth; chemical toolkit (DCLK1-IN-1, resistance mutation G532A, kinase-dead D511N/D533N) established DCLK1 kinase activity regulates RNA processing pathways; CDK11 was identified as a potential DCLK1 substrate by phosphoproteomics. Selective kinase inhibitor (DCLK1-IN-1); resistance mutation G532A; kinase-dead mutants (D511N, D533N); phosphoproteomics; engineered DCLK1-dependent cancer cell line Cell chemical biology High 32755567
2022 DCLK1 binds and phosphorylates XRCC5 (Ku80); phosphorylated XRCC5 transcriptionally activates COX-2, enhancing prostaglandin E2 production and generating a pro-inflammatory tumor microenvironment that drives aggressive colorectal cancer behavior. Comprehensive proteomics/genomics to identify DCLK1 binding partners; Co-IP (DCLK1–XRCC5); in vitro kinase assay (DCLK1 phosphorylates XRCC5); COX-2 transcriptional reporter; CRC mouse models Theranostics High 35910805
2023 Macrophage DCLK1 directly binds IKKβ and phosphorylates IKKβ at S177/181, facilitating NF-κB activation and inflammatory gene expression; macrophage-specific DCLK1 deletion attenuates atherosclerosis and reduces inflammation in ApoE-/- mice. Co-immunoprecipitation; LC-MS/MS identification of IKKβ as DCLK1 binding partner; in vitro phosphorylation assay (DCLK1 phosphorylates IKKβ S177/181); macrophage-specific knockout; RNA-seq; pharmacological inhibition EMBO molecular medicine High 36896602
2023 Macrophage DCLK1 mediates RIP2/TAK1 phosphorylation upon high-fat diet/palmitate challenge, leading to inflammatory cytokine release that promotes cardiac hypertrophy and fibrosis; macrophage-specific (not cardiomyocyte-specific) DCLK1 knockout prevents obesity-induced cardiomyopathy. Macrophage-specific and cardiomyocyte-specific DCLK1 KO mice; high-fat diet model; RNA sequencing; immunoblot for RIP2/TAK1 phosphorylation; pharmacological inhibition Cell death & disease High 37443105
2019 Overexpression of DCLK1-AL (isoform 2/alpha-long) in pancreatic cancer cells increases KRAS activation (demonstrated by RAS pull-down assay) and co-immunoprecipitation confirms DCLK1–KRAS interaction; DCLK1-AL overexpression drives increased invasion and drug resistance downstream of KRAS/PI3K/AKT/mTOR. Lentiviral stable overexpression; RAS pull-down assay; co-immunoprecipitation; Matrigel invasion assay; drug resistance assays; KPC mouse model Journal of oncology Medium 31467540
2019 DCLK1 interacts with CCAR1 through its C-terminal domain and phosphorylates CCAR1 at Ser343, stabilizing CCAR1; DCLK1-mediated CCAR1 stabilization positively regulates β-catenin signaling, maintaining cancer stemness and 5-FU resistance in colorectal cancer. Co-IP (DCLK1–CCAR1); in vitro phosphorylation assay (Ser343 site identified); domain mapping; β-catenin pathway inhibitor rescue; in vitro and in vivo CRC models Clinical and translational medicine Medium 35522902
2015 Human colorectal cancers predominantly express a short DCLK1 isoform (DCLK1-S) from an alternate β-promoter in intron V, while normal colons express DCLK1-L from the 5′(α)-promoter; activated NF-κBp65 drives the β-promoter, whereas β-catenin/TCF4/LEF activates the α-promoter in cancer cells. In silico analysis; molecular biology (promoter cloning, luciferase reporter assay for promoter activity); qRT-PCR in patient cohort Scientific reports Medium 26447334
2021 DCLK1 influences small extracellular vesicle (sEV/exosome) biogenesis in a kinase-dependent manner; DCLK1 overexpression promotes sEV-mediated cell migration, and DCLK1-IN-1 (kinase inhibitor) reverses increases in sEV size/concentration and alters cargo selection of proteins involved in EV biogenesis (KTN1, CHMP1A, MYO1G) and migration/adhesion. DCLK1 overexpression in GC cells; sEV isolation; quantitative proteome analysis; DCLK1-IN-1 kinase inhibitor; migration assay Proteomics Medium 33991177
2021 miR-195 directly interacts with the 3′-UTR of Dclk1 mRNA to inhibit DCLK1 translation; RNA-binding protein HuR competes with miR-195 for Dclk1 mRNA binding and increases DCLK1 expression; transgenic miR-195 overexpression reduces intestinal tuft cell numbers via DCLK1 suppression. miR-195 transgenic mice; intestinal organoids; RNA pulldown/RIP; luciferase 3′-UTR reporter; competition assay between HuR and miR-195 American journal of physiology. Cell physiology High 33788631
2022 DCLK1 promotes CRC immune evasion by upregulating CXCL1, which recruits MDSCs via CXCR2; DCLK1-knockout tumors fail to establish in immune-competent mice due to increased CD8+ T cell infiltration and reduced MDSCs; CXCL1 overexpression rescues DCLK1-/- tumor growth. CRISPR-Cas9 DCLK1 knockout tumor cells; subcutaneous and orthotopic transplantation models; flow cytometry of tumor-infiltrating immune cells; MDSC–T cell co-culture; CXCL1 rescue overexpression; RNA sequencing Cellular and molecular gastroenterology and hepatology High 36309200
2021 DCLK1-isoform2 overexpression in pancreatic cancer cells drives polarization of macrophages from M1 toward immunosuppressive M2 phenotype via secreted chemokines/cytokines; M2-macrophages educated by DCLK1-isoform2 enhance PDAC cell migration, invasion, and self-renewal; DCLK1-isoform2-educated M2 macrophages inhibit CD8+ T-cell proliferation and granzyme-B activation. Stable DCLK1-isoform2 overexpression; macrophage co-culture/polarization assays; organoid-immune cell co-culture; CD8+ T cell activation assays; autochthonous KPCY mouse model Molecular cancer therapeutics Medium 32371580
2021 DCLK1-S short splice variant promotes ESCC progression via MAPK/ERK signaling leading to MMP2 upregulation and EMT activation; ERK1/2 inhibitor SCH772984 attenuates the proliferative and migratory phenotype induced by DCLK1-S. CRISPR/Cas9 DCLK1 total KO with DCLK1-S rescue; RNA-sequencing; KEGG pathway analysis; in vitro migration/invasion assays; in vivo tumor and metastasis models; ERK inhibitor rescue Molecular cancer research Medium 34610960

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Dclk1 distinguishes between tumor and normal stem cells in the intestine. Nature genetics 336 23202126
2013 DCLK1 marks a morphologically distinct subpopulation of cells with stem cell properties in preinvasive pancreatic cancer. Gastroenterology 262 24096005
2016 Dclk1 Defines Quiescent Pancreatic Progenitors that Promote Injury-Induced Regeneration and Tumorigenesis. Cell stem cell 188 27058937
2011 DCAMKL-1 regulates epithelial-mesenchymal transition in human pancreatic cells through a miR-200a-dependent mechanism. Cancer research 182 21285251
2000 DCAMKL1 encodes a protein kinase with homology to doublecortin that regulates microtubule polymerization. The Journal of neuroscience : the official journal of the Society for Neuroscience 166 11124993
2016 Microtubule-binding protein doublecortin-like kinase 1 (DCLK1) guides kinesin-3-mediated cargo transport to dendrites. The EMBO journal 137 26758546
2013 DCLK1 regulates pluripotency and angiogenic factors via microRNA-dependent mechanisms in pancreatic cancer. PloS one 121 24040120
2014 XMD8-92 inhibits pancreatic tumor xenograft growth via a DCLK1-dependent mechanism. Cancer letters 111 24880079
2014 Curcumin promotes autophagic survival of a subset of colon cancer stem cells, which are ablated by DCLK1-siRNA. Cancer research 103 24626093
2011 Gastric tuft cells express DCLK1 and are expanded in hyperplasia. Histochemistry and cell biology 102 21688022
2009 Selective blockade of DCAMKL-1 results in tumor growth arrest by a Let-7a MicroRNA-dependent mechanism. Gastroenterology 101 19445940
2017 Dclk1, a tumor stem cell marker, regulates pro-survival signaling and self-renewal of intestinal tumor cells. Molecular cancer 93 28148261
2015 DCLK1 is a broadly dysregulated target against epithelial-mesenchymal transition, focal adhesion, and stemness in clear cell renal carcinoma. Oncotarget 85 25605241
2018 Dclk1 in tuft cells promotes inflammation-driven epithelial restitution and mitigates chronic colitis. Cell death and differentiation 81 30478383
2017 Dclk1-expressing tuft cells: critical modulators of the intestinal niche? American journal of physiology. Gastrointestinal and liver physiology 80 28684459
2018 DCLK1 promotes epithelial-mesenchymal transition via the PI3K/Akt/NF-κB pathway in colorectal cancer. International journal of cancer 75 29277893
2014 DCLK1 facilitates intestinal tumor growth via enhancing pluripotency and epithelial mesenchymal transition. Oncotarget 73 25211188
2014 Brief report: Dclk1 deletion in tuft cells results in impaired epithelial repair after radiation injury. Stem cells (Dayton, Ohio) 71 24123696
1998 Expression and chromosomal localization of KIAA0369, a putative kinase structurally related to Doublecortin. Journal of human genetics 71 9747029
2016 miR-137 Regulates the Tumorigenicity of Colon Cancer Stem Cells through the Inhibition of DCLK1. Molecular cancer research : MCR 70 26747706
1999 KIAA0369, doublecortin-like kinase, is expressed during brain development. Journal of neuroscience research 69 10533048
2016 Dominant Expression of DCLK1 in Human Pancreatic Cancer Stem Cells Accelerates Tumor Invasion and Metastasis. PloS one 67 26764906
2010 Identification of a novel putative pancreatic stem/progenitor cell marker DCAMKL-1 in normal mouse pancreas. American journal of physiology. Gastrointestinal and liver physiology 66 20522640
2020 Cancer Stem Cell Marker DCLK1 Correlates with Tumorigenic Immune Infiltrates in the Colon and Gastric Adenocarcinoma Microenvironments. Cancers 64 31979136
2018 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. International journal of cancer 63 29577277
2019 The Histone Demethylase KDM3A, Increased in Human Pancreatic Tumors, Regulates Expression of DCLK1 and Promotes Tumorigenesis in Mice. Gastroenterology 62 31442435
2016 Functional implication of Dclk1 and Dclk1-expressing cells in cancer. Small GTPases 60 27458755
2015 Epigenetic changes and alternate promoter usage by human colon cancers for expressing DCLK1-isoforms: Clinical Implications. Scientific reports 60 26447334
2018 Inhibition of LEF1-Mediated DCLK1 by Niclosamide Attenuates Colorectal Cancer Stemness. Clinical cancer research : an official journal of the American Association for Cancer Research 59 30446587
1999 DCAMKL1, a brain-specific transmembrane protein on 13q12.3 that is similar to doublecortin (DCX). Genomics 57 10036192
1999 High expression of doublecortin and KIAA0369 protein in fetal brain suggests their specific role in neuronal migration. The American journal of pathology 57 10550327
2017 MicroRNA-195 Suppresses the Progression of Pancreatic Cancer by Targeting DCLK1. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 55 29224010
2013 The microtubule-associated protein DCAMKL1 regulates osteoblast function via repression of Runx2. The Journal of experimental medicine 54 23918955
2014 The recently suggested intestinal cancer stem cell marker DCLK1 is an epigenetic biomarker for colorectal cancer. Epigenetics 51 24384857
2012 DCLK1 immunoreactivity in colorectal neoplasia. Clinical and experimental gastroenterology 51 22557932
2022 Inhibition of DCLK1 sensitizes resistant lung adenocarcinomas to EGFR-TKI through suppression of Wnt/β-Catenin activity and cancer stemness. Cancer letters 50 35157971
2018 Enhancement of Sensitivity to Chemo/Radiation Therapy by Using miR-15b against DCLK1 in Colorectal Cancer. Stem cell reports 50 30449704
2016 Regulatory Roles of Dclk1 in Epithelial Mesenchymal Transition and Cancer Stem Cells. Journal of carcinogenesis & mutagenesis 49 27335684
2020 Extracellular vesicles-encapsulated let-7i shed from bone mesenchymal stem cells suppress lung cancer via KDM3A/DCLK1/FXYD3 axis. Journal of cellular and molecular medicine 46 33350586
2019 DCLK1 Monoclonal Antibody-Based CAR-T Cells as a Novel Treatment Strategy against Human Colorectal Cancers. Cancers 46 31878090
2015 Plasma DCLK1 is a marker of hepatocellular carcinoma (HCC): Targeting DCLK1 prevents HCC tumor xenograft growth via a microRNA-dependent mechanism. Oncotarget 46 26468984
2016 miR-613 inhibits the growth and invasiveness of human hepatocellular carcinoma via targeting DCLK1. Biochemical and biophysical research communications 45 27049311
2023 Macrophage DCLK1 promotes atherosclerosis via binding to IKKβ and inducing inflammatory responses. EMBO molecular medicine 44 36896602
2017 Modified miR-15a has therapeutic potential for improving treatment of advanced stage colorectal cancer through inhibition of BCL2, BMI1, YAP1 and DCLK1. Oncotarget 44 29416778
2015 Dclk1+ small intestinal epithelial tuft cells display the hallmarks of quiescence and self-renewal. Oncotarget 44 26362399
2020 LncRNA SNHG1 promotes EMT process in gastric cancer cells through regulation of the miR-15b/DCLK1/Notch1 axis. BMC gastroenterology 41 32423385
2018 RETRACTED: miR-539 enhances chemosensitivity to cisplatin in non-small cell lung cancer by targeting DCLK1. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 41 30119173
2021 LncRNA SNHG1 contributes to the cisplatin resistance and progression of NSCLC via miR-330-5p/DCLK1 axis. Experimental and molecular pathology 40 33753110
2020 Tuft and Cancer Stem Cell Marker DCLK1: A New Target to Enhance Anti-Tumor Immunity in the Tumor Microenvironment. Cancers 40 33348546
2021 DCLK1, a Putative Stem Cell Marker in Human Cholangiocarcinoma. Hepatology (Baltimore, Md.) 38 32978808
2005 Expression of doublecortin (DCX) and doublecortin-like kinase (DCLK) within the developing chick brain. Developmental dynamics : an official publication of the American Association of Anatomists 38 15614772
2020 DCLK1 Regulates Tumor Stemness and Cisplatin Resistance in Non-small Cell Lung Cancer via ABCD-Member-4. Molecular therapy oncolytics 37 32637578
2016 DCLK1 phosphorylates the microtubule-associated protein MAP7D1 to promote axon elongation in cortical neurons. Developmental neurobiology 37 27503845
2015 Upregulation of circulating cancer stem cell marker, DCLK1 but not Lgr5, in chemoradiotherapy-treated colorectal cancer patients. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 37 25631749
2020 DCLK1-Isoform2 Alternative Splice Variant Promotes Pancreatic Tumor Immunosuppressive M2-Macrophage Polarization. Molecular cancer therapeutics 36 32371580
2019 DCLK1 Plays a Metastatic-Promoting Role in Human Breast Cancer Cells. BioMed research international 36 31223610
2019 Overexpression of DCLK1-AL Increases Tumor Cell Invasion, Drug Resistance, and KRAS Activation and Can Be Targeted to Inhibit Tumorigenesis in Pancreatic Cancer. Journal of oncology 36 31467540
2017 Pancreatic Neuroendocrine Tumors and EMT Behavior Are Driven by the CSC Marker DCLK1. Molecular cancer research : MCR 36 28179411
2004 Functional differences between two DCLK splice variants. Brain research. Molecular brain research 36 14741399
2021 DCLK1 autoinhibition and activation in tumorigenesis. Innovation (Cambridge (Mass.)) 35 34977835
2016 Intestinal tuft cells regulate the ATM mediated DNA Damage response via Dclk1 dependent mechanism for crypt restitution following radiation injury. Scientific reports 35 27876863
1999 Genomic structure, chromosomal mapping, and expression pattern of human DCAMKL1 (KIAA0369), a homologue of DCX (XLIS). Genomics 35 10051403
2013 Inhibition of Notch signaling reduces the number of surviving Dclk1+ reserve crypt epithelial stem cells following radiation injury. American journal of physiology. Gastrointestinal and liver physiology 34 24368703
2019 Inhibition of DCLK1 down-regulates PD-L1 expression through Hippo pathway in human pancreatic cancer. Life sciences 32 31837335
2022 DCLK1 promotes colorectal cancer stemness and aggressiveness via the XRCC5/COX2 axis. Theranostics 31 35910805
2014 DCLK1 is detectable in plasma of patients with Barrett's esophagus and esophageal adenocarcinoma. Digestive diseases and sciences 31 25283374
2017 A novel antibody against cancer stem cell biomarker, DCLK1-S, is potentially useful for assessing colon cancer risk after screening colonoscopy. Laboratory investigation; a journal of technical methods and pathology 30 28414327
2022 Targeting DCLK1 overcomes 5-fluorouracil resistance in colorectal cancer through inhibiting CCAR1/β-catenin pathway-mediated cancer stemness. Clinical and translational medicine 28 35522902
2016 Survival of Patients with Gastrointestinal Cancers Can Be Predicted by a Surrogate microRNA Signature for Cancer Stem-like Cells Marked by DCLK1 Kinase. Cancer research 28 27287716
2021 Inhibition of DCLK1 with DCLK1-IN-1 Suppresses Renal Cell Carcinoma Invasion and Stemness and Promotes Cytotoxic T-Cell-Mediated Anti-Tumor Immunity. Cancers 26 34830884
2015 Inflammatory and oncogenic roles of a tumor stem cell marker doublecortin-like kinase (DCLK1) in virus-induced chronic liver diseases. Oncotarget 26 25948779
2022 Pleiotropic effects of DCLK1 in cancer and cancer stem cells. Frontiers in molecular biosciences 25 36250024
2021 Cancer stem cell marker DCLK1 reprograms small extracellular vesicles toward migratory phenotype in gastric cancer cells. Proteomics 25 33991177
2021 MicroRNA-195 regulates Tuft cell function in the intestinal epithelium by altering translation of DCLK1. American journal of physiology. Cell physiology 24 33788631
2021 Structural basis for small molecule targeting of Doublecortin Like Kinase 1 with DCLK1-IN-1. Communications biology 24 34545159
2016 Epigenetic regulation of human DCLK-1 gene during colon-carcinogenesis: clinical and mechanistic implications. Stem cell investigation 24 27777940
2023 Macrophage DCLK1 promotes obesity-induced cardiomyopathy via activating RIP2/TAK1 signaling pathway. Cell death & disease 23 37443105
2022 Inhibition of DCLK1 kinase reverses epithelial-mesenchymal transition and restores T-cell activity in pancreatic ductal adenocarcinoma. Translational oncology 23 34998236
2012 DCLK1 variants are associated across schizophrenia and attention deficit/hyperactivity disorder. PloS one 23 22539971
2018 DCLK1 plays an important role in colorectal cancer tumorgenesis through the regulation of miR-200c. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 22 29656186
2016 Evaluation of circulating cellular DCLK1 protein, as the most promising colorectal cancer stem cell marker, using immunoassay based methods. Cancer biomarkers : section A of Disease markers 22 27802206
2012 Immunolocalization of DCAMKL-1, a putative intestinal stem cell marker, in normal colonic tissue. Pathology, research and practice 22 22749579
2010 Altered expression of a putative progenitor cell marker DCAMKL1 in the rat gastric mucosa in regeneration, metaplasia and dysplasia. BMC gastroenterology 22 20565818
2023 Targeting DCLK1 attenuates tumor stemness and evokes antitumor immunity in triple-negative breast cancer by inhibiting IL-6/STAT3 signaling. Breast cancer research : BCR 21 37069669
2018 Dclk1 Inhibition Cancels 5-FU-induced Cell-cycle Arrest and Decreases Cell Survival in Colorectal Cancer. Anticancer research 21 30396941
2021 Doublecortin-Like Kinase 1 (DCLK1) Is a Novel NOTCH Pathway Signaling Regulator in Head and Neck Squamous Cell Carcinoma. Frontiers in oncology 20 34336664
2019 Increased expression of DCLK1, a novel putative CSC maker, is associated with tumor aggressiveness and worse disease-specific survival in patients with bladder carcinomas. Experimental and molecular pathology 20 31028726
2019 DCLK1 promotes malignant progression of breast cancer by regulating Wnt/β-Catenin signaling pathway. European review for medical and pharmacological sciences 20 31773701
2021 DCLK1-Short Splice Variant Promotes Esophageal Squamous Cell Carcinoma Progression via the MAPK/ERK/MMP2 Pathway. Molecular cancer research : MCR 19 34610960
2020 Synthesis and Structure-Activity Relationships of DCLK1 Kinase Inhibitors Based on a 5,11-Dihydro-6H-benzo[e]pyrimido[5,4-b][1,4]diazepin-6-one Scaffold. Journal of medicinal chemistry 19 32530623
2016 Potential Mechanism of Neurite Outgrowth Enhanced by Electrical Stimulation: Involvement of MicroRNA-363-5p Targeting DCLK1 Expression in Rat. Neurochemical research 19 27900578
2022 Long noncoding RNA BMPR1B-AS1 facilitates endometrial cancer cell proliferation and metastasis by sponging miR-7-2-3p to modulate the DCLK1/Akt/NF-κB pathway. Cell cycle (Georgetown, Tex.) 18 35404759
2022 DCLK1 Suppresses Tumor-Specific Cytotoxic T Lymphocyte Function Through Recruitment of MDSCs via the CXCL1-CXCR2 Axis. Cellular and molecular gastroenterology and hepatology 18 36309200
2021 DCLK1 isoforms and aberrant Notch signaling in the regulation of human and murine colitis. Cell death discovery 18 34226497
2008 Alternative transcripts of Dclk1 and Dclk2 and their expression in doublecortin knockout mice. Developmental neuroscience 18 18075264
2021 DCLK1 and its interaction partners: An effective therapeutic target for colorectal cancer. Oncology letters 17 34733368
2020 Chemical Biology Toolkit for DCLK1 Reveals Connection to RNA Processing. Cell chemical biology 17 32755567
2018 Pancreatic DCLK1+ cells originate distinctly from PDX1+ progenitors and contribute to the initiation of intraductal papillary mucinous neoplasm in mice. Cancer letters 17 29526803
2017 Enhancement of cytotoxic effects of gemcitabine by Dclk1 inhibition through suppression of Chk1 phosphorylation in human pancreatic cancer cells. Oncology reports 16 29048622
2013 Expression of LGR-5, MSI-1 and DCAMKL-1, putative stem cell markers, in the early phases of 1,2-dimethylhydrazine-induced rat colon carcinogenesis: correlation with nuclear β-catenin. BMC cancer 16 23374535