ArticleeLife2015
Phosphodiesterase 4D acts downstream of Neuropilin to control Hedgehog signal transduction and the growth of medulloblastoma.
Article in eLife, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 42 citations in OpenAlex.
- Hedgehog pathway, cell cycle, and primary cilium.Cell death discovery · 2025Review
- PDE4D drives rewiring of the MAPK pathway in BRAF-mutated melanoma resistant to MAPK inhibitors.Cell communication and signaling : CCS · 2024Article
- Semaphorin Receptors Antagonize Wnt Signaling Through Beta-Catenin Degradation.bioRxiv : the preprint server for biology · 2024Article
- A Benzarone Derivative Inhibits EYA to Suppress Tumor Growth in SHH Medulloblastoma.Cancer research · 2024Article
- cAMP-PKA/EPAC signaling and cancer: the interplay in tumor microenvironment.Journal of hematology & oncology · 2024Review
- Hedgehog Signaling in Cortical Development.Cells · 2023Review
- Article
- Control of the Hedgehog pathway by compartmentalized PKA in the primary cilium.Science China. Life sciences · 2022Review
- Dissection of the microRNA Network Regulating Hedgehog Signaling inFrontiers in cell and developmental biology · 2022Article
- Myomegalin regulates Hedgehog pathway by controlling PDE4D at the centrosome.Molecular biology of the cell · 2021Article
- Medulloblastoma drugs in development: Current leads, trials and drawbacks.European journal of medicinal chemistry · 2021Review
- Neuropilin-1: A Key Protein to Consider in the Progression of Pediatric Brain Tumors.Frontiers in oncology · 2021Review
- Complex roles of cAMP-PKA-CREB signaling in cancer.Experimental hematology & oncology · 2020Review
- Transient Primary Cilia Mediate Robust Hedgehog Pathway-Dependent Cell Cycle Control.Current biology : CB · 2020Article
- Biochemical mechanisms of vertebrate hedgehog signaling.Development (Cambridge, England) · 2019Review
- Inhibition of phosphodiesterase 4D decreases the malignant properties of DLD-1 colorectal cancer cells by repressing the AKT/mTOR/Myc signaling pathway.Oncology letters · 2019Article
- Neuropilins in the Context of Tumor Vasculature.International journal of molecular sciences · 2019Review
- Developmental phosphoproteomics identifies the kinase CK2 as a driver of Hedgehog signaling and a therapeutic target in medulloblastoma.Science signaling · 2018Article
- A comprehensive analysis of the predicted targets of miR-642b-3p associated with the long non-coding RNA HOXA11-AS in NSCLC cells.Oncology letters · 2018Article
- The role of the Hedgehog signaling pathway in cancer: A comprehensive review.Bosnian journal of basic medical sciences · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Alterations in Hedgehog (Hh) signaling lead to birth defects and cancers including medulloblastoma, the most common pediatric brain tumor. Although inhibitors targeting the membrane protein Smoothened suppress Hh signaling, acquired drug resistance and tumor relapse call for additional therapeutic targets. Here we show that phosphodiesterase 4D (PDE4D) acts downstream of Neuropilins to control Hh transduction and medulloblastoma growth. PDE4D interacts directly with Neuropilins, positive regulators of Hh pathway. The Neuropilin ligand Semaphorin3 enhances this interaction, promoting PDE4D translocation to the plasma membrane and cAMP degradation. The consequent inhibition of protein kinase A (PKA) enhances Hh transduction. In the developing cerebellum, genetic removal of Neuropilins reduces Hh signaling activity and suppresses proliferation of granule neuron precursors. In mouse medulloblastoma allografts, PDE4D inhibitors suppress Hh transduction and inhibit tumor growth. Our findings reveal a new regulatory mechanism of Hh transduction, and highlight PDE4D as a promising target to treat Hh-related tumors.
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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.