ArticleOncotarget2017
DYRK1B blocks canonical and promotes non-canonical Hedgehog signaling through activation of the mTOR/AKT pathway.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
50 citing papers in PubMed, 77 citations in OpenAlex.
- Small-Molecule-Mediated Depletion of the Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase 1B (DYRK1B) Protein Scaffold.ACS pharmacology & translational science · 2026Article
- Review
- Non-cell-autonomous regulation of mTORC2 by Hedgehog signaling maintains lipid homeostasis.Cell reports · 2025Article
- Rapid effects of valproic acid on the fetal brain transcriptome: implications for brain development and autism.Translational psychiatry · 2024Article
- Article
- Identification and functional validation of rare coding variants in genes linked to monogenic obesity.Obesity (Silver Spring, Md.) · 2024Article
- Effects of Isoxazolyl Steroids on Key Genes of Sonic Hedgehog Cascade Expression in Tumor Cells.Molecules (Basel, Switzerland) · 2024Article
- Article
- Mirk/Dyrk1B Kinase Inhibitors in Targeted Cancer Therapy.Pharmaceutics · 2024Review
- Mirk/Dyrk1B controls ventral spinal cord development via Shh pathway.Cellular and molecular life sciences : CMLS · 2024Article
- Rapid effects of valproic acid on the fetal brain transcriptome: Implications for brain development and autism.Research square · 2024Article
- Super-enhancer hijacking drives ectopic expression of hedgehog pathway ligands in meningiomas.Nature communications · 2023Article
- CMGC Kinases in Health and Cancer.Cancers · 2023Review
- Hedgehog-GLI mediated control of renal formation and malformation.Frontiers in nephrology · 2023Review
- The role of Hedgehog and Notch signaling pathway in cancer.Molecular biomedicine · 2022Review
- A toolkit for the identification of NEAT1_2/paraspeckle modulators.Nucleic acids research · 2022Article
- Basal Cell Carcinoma: Pathology, Current Clinical Treatment, and Potential Use of Lipid Nanoparticles.Cancers · 2022Review
- A Bioinformatics Evaluation of the Role of Dual-Specificity Tyrosine-Regulated Kinases in Colorectal Cancer.Cancers · 2022Article
- Hedgehog/GLI signaling in hematopoietic development and acute myeloid leukemia-From bench to bedside.Frontiers in cell and developmental biology · 2022Review
- Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hedgehog (Hh) signaling plays important roles in embryonic development and in tumor formation. Apart from the well-established stimulation of the GLI family of transcription factors, Hh ligands promote the phosphorylation and activation of mTOR and AKT kinases, yet the molecular mechanism underlying these processes are unknown. Here, we identify the DYRK1B kinase as a mediator between Hh signaling and mTOR/AKT activation. In fibroblasts, Hh signaling induces DYRK1B protein expression, resulting in activation of the mTOR/AKT kinase signaling arm. Furthermore, DYRK1B exerts positive and negative feedback regulation on the Hh pathway itself: It negatively interferes with SMO-elicited canonical Hh signaling, while at the same time it provides positive feed-forward functions by promoting AKT-mediated GLI stability. Due to the fact that the mTOR/AKT pathway is itself subject to strong negative feedback regulation, pharmacological inhibition of DYRK1B results in initial upregulation followed by downregulation of AKT phosphorylation and GLI stabilization. Addressing this issue therapeutically, we show that a pharmacological approach combining a DYRK1B antagonist with an mTOR/AKT inhibitor results in strong GLI1 targeting and in pronounced cytotoxicity in human pancreatic and ovarian cancer cells.
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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.