ArticleOncotarget2016
The energy sensor AMPK regulates Hedgehog signaling in human cells through a unique Gli1 metabolic checkpoint.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 44 citations in OpenAlex.
- Hedgehog/GLI Signaling at the Interface of Sterol Metabolism, Mitochondrial ROS Signaling and Cellular Plasticity.Antioxidants (Basel, Switzerland) · 2026Review
- Brain-Targeted Delivery of Phenformin Using Phospholipid and Non-Phospholipid Vesicles for SHH Medulloblastoma.Nanomaterials (Basel, Switzerland) · 2026Article
- SALL4 is a CRL3Cell death and differentiation · 2024Article
- Pharmacological targeting of smoothened receptor cysteine-rich domain by Budesonide promotesFrontiers in molecular neuroscience · 2024Article
- Understanding the Roles of the Hedgehog Signaling Pathway during T-Cell Lymphopoiesis and in T-Cell Acute Lymphoblastic Leukemia (T-ALL).International journal of molecular sciences · 2023Review
- Review
- Cilia-localized GID/CTLH ubiquitin ligase complex regulates protein homeostasis of sonic hedgehog signaling components.Journal of cell science · 2022Article
- Isoforms of the orphan nuclear receptor COUP‑TFII differentially modulate pancreatic cancer progression.International journal of oncology · 2022Article
- Wheel running improves fasting-induced AMPK signaling in skeletal muscle from tumor-bearing mice.Physiological reports · 2021Article
- Responsiveness to Hedgehog Pathway Inhibitors in T-Cell Acute Lymphoblastic Leukemia Cells Is Highly Dependent on 5'AMP-Activated Kinase Inactivation.International journal of molecular sciences · 2021Article
- Activation of AMPK sensitizes medulloblastoma to Vismodegib and overcomes Vismodegib-resistance.FASEB bioAdvances · 2021Article
- Blockade of EIF5A hypusination limits colorectal cancer growth by inhibiting MYC elongation.Cell death & disease · 2020Article
- Gorlin Syndrome: Recent Advances in Genetic Testing and Molecular and Cellular Biological Research.International journal of molecular sciences · 2020Review
- Hedgehog Signaling and Truncated GLI1 in Cancer.Cells · 2020Review
- Article
- Clobetasol propionate enhances neural stem cell and oligodendrocyte differentiation.Experimental and therapeutic medicine · 2019Article
- Role of Protein Kinases in Hedgehog Pathway Control and Implications for Cancer Therapy.Cancers · 2019Review
- Polyamine Metabolism as a Therapeutic Target inHedgehog-Driven Basal Cell Carcinomaand Medulloblastoma.Cells · 2019Review
- Mitogen-activated kinase kinase kinase 1 inhibits hedgehog signaling and medulloblastoma growth through GLI1 phosphorylation.International journal of oncology · 2019Article
- Non-canonical Hedgehog Signaling Pathway in Cancer: Activation of GLI Transcription Factors Beyond Smoothened.Frontiers in genetics · 2019Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hedgehog signaling controls proliferation of cerebellar granule cell precursors (GCPs) and its aberrant activation is a leading cause of Medulloblastoma, the most frequent pediatric brain tumor. We show here that the energy sensor AMPK inhibits Hh signaling by phosphorylating a single residue of human Gli1 that is not conserved in other species. Studies with selective agonists and genetic deletion have revealed that AMPK activation inhibits canonical Hh signaling in human, but not in mouse cells. Indeed we show that AMPK phosphorylates Gli1 at the unique residue Ser408, which is conserved only in primates but not in other species. Once phosphorylated, Gli1 is targeted for proteasomal degradation. Notably, we show that selective AMPK activation inhibits Gli1-driven proliferation and that this effect is linked to Ser408 phosphorylation, which represents a key metabolic checkpoint for Hh signaling. Collectively, this data unveil a novel mechanism of inhibition of Gli1 function, which is exclusive for human cells and may be exploited for the treatment of Medulloblastoma or other Gli1 driven 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.