ArticleThe Journal of biological chemistry2015
A Functional and Putative Physiological Role of Calcitriol in Patched1/Smoothened Interaction.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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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
8 citing papers in PubMed, 19 citations in OpenAlex.
- Understanding Abnormal SMO-SHH Signaling in Autism Spectrum Disorder: Potential Drug Target and Therapeutic Goals.Cellular and molecular neurobiology · 2022Review
- Calcitriol Promotes Differentiation of Glioma Stem-Like Cells and Increases Their Susceptibility to Temozolomide.Cancers · 2021Article
- Recent Advances in Signaling Pathways Comprehension as Carcinogenesis Triggers in Basal Cell Carcinoma.Journal of clinical medicine · 2020Review
- Article
- Skin-Derived Vitamin DThe Journal of investigative dermatology · 2017Article
- Sonidegib: mechanism of action, pharmacology, and clinical utility for advanced basal cell carcinomas.OncoTargets and therapy · 2017Review
- Differential Cellular Responses to Hedgehog Signalling in Vertebrates-What is the Role of Competence?Journal of developmental biology · 2016Review
- Article
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 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Patched1 (Ptch)-mediated inhibition of Smoothened (Smo) is still an open question. However, a direct Ptch/Smo interaction has been excluded, Smo modulators were identified, but the endogenous signal transmitting molecule remains undiscovered. Here, we demonstrate that calcitriol, the hormonally active form of vitamin D3, is an excellent candidate for transmission of Ptch/Smo interaction. Our study reveals that Ptch expression is sufficient to release calcitriol from the cell and that calcitriol inhibits Smo action and ciliary translocation by acting on a site distinct from the 7-transmembrane domain or the cysteine-rich domain. Moreover calcitriol strongly synergizes with itraconazole (ITZ) in Smo inhibition, which did not result from elevated calcitriol bioavailability due to ITZ-mediated 24-hydroxylase inhibition but rather from a direct interaction of the compounds at the level of Smo. Together, we suggest that calcitriol represents a possible endogenous transmitter of Ptch/Smo interaction. Moreover calcitriol or calcitriol derivatives combined with ITZ might be a treatment option of Hedgehog-associated cancers.
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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.