ArticleProceedings of the National Academy of Sciences of the United States of America2006
Oxysterols stimulate Sonic hedgehog signal transduction and proliferation of medulloblastoma cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 158 papers.
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Who cites it
158 citing papers in PubMed, 313 citations in OpenAlex.
- Metabolic programming in tooth development: a regulatory network from energy substrates to signaling instructions.Frontiers in cell and developmental biology · 2026Review
- Unveiling the potential benefits of statins in medulloblastoma treatment: A promising therapeutic approach.IBRO neuroscience reports · 2025Review
- Discovery of a novel regulator, 3β-sulfate-5-cholestenoic acid, of lipid metabolism and inflammation.American journal of physiology. Endocrinology and metabolism · 2025Article
- Review
- Cilia-enriched oxysterol 7β,27-DHC is required for polycystin ion channel activation.Nature communications · 2024Article
- PTCH1-mutant human cerebellar organoids exhibit altered neural development and recapitulate early medulloblastoma tumorigenesis.Disease models & mechanisms · 2024Article
- Non-canonical non-genomic morphogen signaling in anucleate platelets: a critical determinant of prothrombotic function in circulation.Cell communication and signaling : CCS · 2024Review
- Roles of clinical application of lenvatinib and its resistance mechanism in advanced hepatocellular carcinoma (Review).American journal of cancer research · 2024Review
- 25-Hydroxycholesterol in health and diseases.Journal of lipid research · 2024Review
- Cellular and molecular mechanisms of Hedgehog signalling.Nature reviews. Molecular cell biology · 2023Review
- The Potential Therapeutic Application of Simvastatin for Brain Complications and Mechanisms of Action.Pharmaceuticals (Basel, Switzerland) · 2023Review
- The Inseparable Relationship Between Cholesterol and Hedgehog Signaling.Annual review of biochemistry · 2023Review
- Sonic Hedgehog Signaling Pathway: A Role in Pain Processing.Neurochemical research · 2023Review
- Lipid metabolism of hepatocellular carcinoma impacts targeted therapy and immunotherapy.World journal of gastrointestinal oncology · 2023Review
- Activation mechanism of the human Smoothened receptor.Biophysical journal · 2023Article
- 7-Dehydrocholesterol-derived oxysterols cause neurogenic defects in Smith-Lemli-Opitz syndrome.eLife · 2022Article
- TPT1 Supports Proliferation of Neural Stem/Progenitor Cells and Brain Tumor Initiating Cells Regulated by Macrophage Migration Inhibitory Factor (MIF).Neurochemical research · 2022Article
- Individual and simultaneous treatment with antipsychotic aripiprazole and antidepressant trazodone inhibit sterol biosynthesis in the adult brain.Journal of lipid research · 2022Article
- Understanding Abnormal SMO-SHH Signaling in Autism Spectrum Disorder: Potential Drug Target and Therapeutic Goals.Cellular and molecular neurobiology · 2022Review
- Control of the Hedgehog pathway by compartmentalized PKA in the primary cilium.Science China. Life sciences · 2022Review
98 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Sterol synthesis is required for Sonic hedgehog (Shh) signal transduction. Errors in Shh signal transduction play important roles in the formation of human tumors, including medulloblastoma (MB). It is not clear which products of sterol synthesis are necessary for Shh signal transduction or how they act. Here we show that cholesterol or specific oxysterols are the critical products of sterol synthesis required for Shh pathway signal transduction in MB cells. In MB cells, sterol synthesis inhibitors reduce Shh target gene transcription and block Shh pathway-dependent proliferation. These effects of sterol synthesis inhibitors can be reversed by exogenous cholesterol or specific oxysterols. We also show that certain oxysterols can maximally activate Shh target gene transcription through the Smoothened (Smo) protein as effectively as the known Smo full agonist, SAG. Thus, sterols are required and sufficient for Shh pathway activation. These results suggest that oxysterols may be critical regulators of Smo, and thereby Shh signal transduction. Inhibition of Shh signaling by sterol synthesis inhibitors may offer a novel approach to the treatment of MB and other Shh pathway-dependent human 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.