ArticleOncotarget2016
Diet-derived 25-hydroxyvitamin D3 activates vitamin D receptor target gene expression and suppresses EGFR mutant non-small cell lung cancer growth in vitro and in vivo.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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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
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Role of VDR gene polymorphisms and environmental factors in the development of skin cancers: evidence by updated meta-analysis.Archives of dermatological research · 2025Pooled it
- Vitamin D Status, Cardiovascular Risk Profile, and miRNA-21 Levels in Hypertensive Patients: Results of the HYPODD Study.Nutrients · 2022Trial
- The impact of vitamin D supplementation on VDR gene expression and body composition in monozygotic twins: randomized controlled trial.Scientific reports · 2020Trial
- Does Consuming Fresh Ultraviolet Light-Exposed Mushrooms Offset the Seasonal Decline in Serum Total 25OHD in Adults Classified as Overweight and Class I Obese? Results from a Randomized Controlled Trial.Foods (Basel, Switzerland) · 2026Article
- Evidence for a role of calcium and vitamin D in the regulation of manganese homeostasis and in the prevention or management of manganese-induced disease.American journal of physiology. Endocrinology and metabolism · 2026Article
- Lifestyle-Based Approaches to Cancer Prevention and Treatment: Diet, Physical Activity, and Integrative Strategies.Pathophysiology : the official journal of the International Society for Pathophysiology · 2025Review
- 4-Hydroxy-1α,25-Dihydroxyvitamin DBiomolecules · 2024Article
- Vitamin D3 improved hypoxia-induced lung injury by inhibiting the complement and coagulation cascade and autophagy pathway.BMC pulmonary medicine · 2024Article
- Cancer Prevention and Treatment Based on Lifestyles.Cancer treatment and research · 2024Review
- Article
- Interplay between Vitamin D and Sphingolipids in Cardiometabolic Diseases.International journal of molecular sciences · 2023Review
- Calcifediol: Why, When, How Much?Pharmaceuticals (Basel, Switzerland) · 2023Review
- Maternal Epidermal Growth Factor Promotes Neonatal Claudin-2 Dependent Increases in Small Intestinal Calcium Permeability.Function (Oxford, England) · 2023Article
- Association between Vitamin D Supplementation and Cancer Mortality: A Systematic Review and Meta-Analysis.Cancers · 2022Review
- Robust osteogenic efficacy of 2α-heteroarylalkyl vitamin D analogue AH-1 in VDR (R270L) hereditary vitamin D-dependent rickets model rats.Scientific reports · 2022Article
- Prediagnostic serum 25-hydroxyvitamin D and melanoma risk.Scientific reports · 2020Article
- Role of glucuronidated 25-hydroxyvitamin D on colon gene expression in mice.American journal of physiology. Gastrointestinal and liver physiology · 2020Article
- Vitamin D status in cats with cardiomyopathy.Journal of veterinary internal medicine · 2020Article
- Vitamin D3 Metabolites Demonstrate Prognostic Value inCancers · 2020Article
- Oral 25-Hydroxycholecalciferol Acts as an Agonist in the Duodenum of Mice and as Modeled in Cultured Human HT-29 and Caco2 Cells.The Journal of nutrition · 2020Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Epidemiologic studies implicate vitamin D status as a factor that influences growth of EGFR mutant lung cancers. However, laboratory based evidence of the biological effect of vitamin D in this disease is lacking. To fill this knowledge gap, we determined vitamin D receptor (VDR) expression in human lung tumors using a tissue microarray constructed of lung cancer cases from never-smokers (where EGFR gene mutations are prevalent). Nuclear VDR was detected in 19/19 EGFR mutant tumors. Expression tended to be higher in tumors with EGFR exon 19 deletions than those with EGFR L858R mutations. To study anti-proliferative activity and signaling, EGFR mutant lung cancer cells were treated with the circulating metabolite of vitamin D, 25-hydroxyvitamin D3 (25D3). 25D3 inhibited clonogenic growth in a dose-dependent manner. CYP27B1 encodes the 1α-hydroxylase (1αOHase) that converts 25D3 to the active metabolite, 1,25-dihydroxyvitamin D3 (1,25D3). Studies employing VDR siRNA, CYP27B1 zinc finger nucleases, and pharmacologic inhibitors of the vitamin D pathway indicate that 25D3 regulates gene expression in a VDR-dependent manner but does not strictly require 1αOHase-mediated conversion of 25D3 to 1,25D3. To determine the effects of modulating serum 25D3 levels on growth of EGFR mutant lung tumor xenografts, mice were fed diets containing 100 or 10,000 IU vitamin D3/kg. High dietary vitamin D3 intake resulted in elevated serum 25D3 and significant inhibition of tumor growth. No toxic effects of supplementation were observed. These results identify EGFR mutant lung cancer as a vitamin D-responsive disease and diet-derived 25D3 as a direct VDR agonist and therapeutic agent.
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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.