ArticleClinical cancer research : an official journal of the American Association for Cancer Research2014
The renin-angiotensin system mediates EGF receptor-vitamin d receptor cross-talk in colitis-associated colon cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 52 citations in OpenAlex.
- Article
- Synergistic Anticancer Effects of Vitamin D and Plant-Derived Compounds: Molecular Mechanisms, Therapeutic Potential, and Nanotechnology-Enabled Delivery Approaches.International journal of molecular sciences · 2026Review
- Vitamin D Receptor in Cancer: Biological Functions, Mechanistic Insights, and Clinical Relevance.Cancer management and research · 2026Review
- VDR Decrease Enhances the Efficacy of 1,25-Dihydroxyvitamin D3 Inhibiting Gefitinib Resistance by Regulating EGFR/FASN Loop in NSCLC Cells.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Dietary Vitamin D Supplementation Improves Hair Follicle Development and Affects Fatty Acid Metabolism in Rex Rabbits.Food science & nutrition · 2025Article
- Tumor-associated macrophages in colon cancer immunotherapy: mechanisms, natural product interventions, and microenvironment remodeling.Frontiers in immunology · 2025Review
- Rethinking corticosteroids use in oncology.Frontiers in pharmacology · 2025Article
- VDR is a potential prognostic biomarker and positively correlated with immune infiltration: a comprehensive pan-cancer analysis with experimental verification.Bioscience reports · 2024Article
- Therapeutic potential of Xihuang Pill in colorectal cancer: Metabolomic and microbiome-driven approaches.Frontiers in pharmacology · 2024Article
- Therapeutic Potential of a Small-Molecule STAT3 Inhibitor in a Mouse Model of Colitis.Cancers · 2023Article
- Longitudinal examination of perfusion and angiogenesis markers in primary colorectal tumors shows distinct signatures for metronomic and maximum-tolerated dose strategies.Neoplasia (New York, N.Y.) · 2022Article
- Review
- Review
- Vitamin D Deficiency Exacerbates Colonic Inflammation Due to Activation of the Local Renin-Angiotensin System in the Colon.Digestive diseases and sciences · 2021Article
- Review
- Effect of Chronic Vitamin D Deficiency on the Development and Severity of DSS-Induced Colon Cancer inComparative medicine · 2020Article
- Vitamin D and Its Potential Interplay With Pain Signaling Pathways.Frontiers in immunology · 2020Review
- Decreased vitamin D receptor protein expression is associated with progression and poor prognosis of colorectal cancer patients.International journal of clinical and experimental pathology · 2020Article
- Losartan and Vitamin D Inhibit Colonic Tumor Development in a Conditional Apc-Deleted Mouse Model of Sporadic Colon Cancer.Cancer prevention research (Philadelphia, Pa.) · 2019Article
- Early increase in blood supply (EIBS) is associated with tumor risk in the Azoxymethane model of colon cancer.BMC cancer · 2018Article
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17 authors at 1 institution in 1 country.
Funding
Abstract
purposeWe previously showed that EGF receptor (EGFR) promotes tumorigenesis in the azoxymethane/dextran sulfate sodium (AOM/DSS) model, whereas vitamin D suppresses tumorigenesis. EGFR-vitamin D receptor (VDR) interactions, however, are incompletely understood. Vitamin D inhibits the renin-angiotensin system (RAS), whereas RAS can activate EGFR. We aimed to elucidate EGFR-VDR cross-talk in colorectal carcinogenesis. EXPERIMENTAL
designTo examine VDR-RAS interactions, we treated Vdr(+/+) and Vdr(-/-) mice with AOM/DSS. Effects of VDR on RAS and EGFR were examined by Western blotting, immunostaining, and real-time PCR. We also examined the effect of vitamin D3 on colonic RAS in Vdr(+/+) mice. EGFR regulation of VDR was examined in hypomorphic Egfr(Waved2) (Wa2) and Egfr(wild-type) mice. Angiotensin II (Ang II)-induced EGFR activation was studied in cell culture.
resultsVdr deletion significantly increased tumorigenesis, activated EGFR and β-catenin signaling, and increased colonic RAS components, including renin and angiotensin II. Dietary VD3 supplementation suppressed colonic renin. Renin was increased in human colon cancers. In studies in vitro, Ang II activated EGFR and stimulated colon cancer cell proliferation by an EGFR-mediated mechanism. Ang II also activated macrophages and colonic fibroblasts. Compared with tumors from Egfr(Waved2) mice, tumors from Egfr(wild-type) mice showed upregulated Snail1, a suppressor of VDR, and downregulated VDR.
conclusionsVDR suppresses the colonic RAS cascade, limits EGFR signals, and inhibits colitis-associated tumorigenesis, whereas EGFR increases Snail1 and downregulates VDR in colonic tumors. Taken together, these results uncover a RAS-dependent mechanism mediating EGFR and VDR cross-talk in colon cancer.
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