ArticleOncogene2013
Imiquimod directly inhibits Hedgehog signalling by stimulating adenosine receptor/protein kinase A-mediated GLI phosphorylation.
Article in Oncogene, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
40 citing papers in PubMed, 77 citations in OpenAlex.
- Local Chemotherapy of Skin Pre-Neoplastic Lesions and Malignancies from the Perspective of Current Pharmaceutics.Pharmaceutics · 2025Review
- Recent developments in peptide vaccines against Glioblastoma, a review and update.Molecular brain · 2025Review
- Ablative fractional laser treatment reduces hedgehog pathway gene expression in murine basal cell carcinomas.Lasers in medical science · 2024Article
- Isostearic acid is an active component of imiquimod formulations used to induce psoriaform disease models.Inflammopharmacology · 2023Article
- Hippo signaling activates hedgehog signaling by Taz-driven Gli3 processing.Cell regeneration (London, England) · 2023Article
- The role of Hedgehog and Notch signaling pathway in cancer.Molecular biomedicine · 2022Review
- Molecular mechanisms underlying the action of carcinogens in gastric cancer with a glimpse into targeted therapy.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- Topical Delivery of Hedgehog Inhibitors: Current Status and Perspectives.International journal of molecular sciences · 2022Review
- Hedgehog Pathway Inhibitors as Targeted Cancer Therapy and Strategies to Overcome Drug Resistance.International journal of molecular sciences · 2022Review
- Distinct trans-placental effects of maternal immune activation by TLR3 and TLR7 agonists: implications for schizophrenia risk.Scientific reports · 2021Article
- Review
- Toll-like receptors and toll-like receptor-targeted immunotherapy against glioma.Journal of hematology & oncology · 2021Review
- Molecular alterations in basal cell carcinoma subtypes.Scientific reports · 2021Article
- Targeting the purinergic pathway in breast cancer and its therapeutic applications.Purinergic signalling · 2021Review
- Treatment of Cutaneous Melanoma Harboring SMO p.Gln216Arg Mutation with Imiquimod: An Old Drug with New Results.Journal of personalized medicine · 2021Article
- Interferon and Toll-Like Receptor 7 Response in COVID-19: Implications of Topical Imiquimod for Prophylaxis and Treatment.Dermatology (Basel, Switzerland) · 2021Review
- Activation of Toll-like receptor 7 provides cardioprotection in septic cardiomyopathy-induced systolic dysfunction.Clinical and translational medicine · 2021Article
- Basal Cell Carcinoma: From Pathophysiology to Novel Therapeutic Approaches.Biomedicines · 2020Review
- Hedgehog/GLI signaling in tumor immunity - new therapeutic opportunities and clinical implications.Cell communication and signaling : CCS · 2019Review
- Role of Protein Kinases in Hedgehog Pathway Control and Implications for Cancer Therapy.Cancers · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Imiquimod (IMQ), a nucleoside analogue of the imidazoquinoline family, is used in the topical treatment of basal cell carcinoma (BCC) and other skin diseases. It is reported to be a TLR7 and TLR8 agonist and, as such, initiates a Th1 immune response by activating sentinel cells in the vicinity of the tumour. BCC is a hedgehog (HH)-driven malignancy with oncogenic glioma-associated oncogene (GLI) signalling activated in a ligand-independent manner. Here we show that IMQ can also directly repress HH signalling by negatively modulating GLI activity in BCC and medulloblastoma cells. Further, we provide evidence that the repressive effect of IMQ on HH signalling is not dependent on TLR/MYD88 signalling. Our results suggest a mechanism for IMQ engaging adenosine receptors (ADORAs) to control GLI signalling. Pharmacological activation of ADORA with either an ADORA agonist or IMQ resulted in a protein kinase A (PKA)-mediated GLI phosphorylation and reduction in GLI activator levels. The activation of PKA and HH pathway target gene downregulation in response to IMQ were abrogated by ADORA inhibition. Furthermore, activated Smoothened signalling, which positively signals to GLI transcription factors, could be effectively counteracted by IMQ. These results reveal a previously unknown mode of action of IMQ in the treatment of BCC and also suggest a role for ADORAs in the regulation of oncogenic HH signalling.
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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.