ArticleInternational journal of cancer2014
Calcium-sensing receptor silencing in colorectal cancer is associated with promoter hypermethylation and loss of acetylation on histone 3.
Article in International journal of cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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
18 citing papers in PubMed, 39 citations in OpenAlex.
- Molecular regulation of calcium-sensing receptor (CaSR)-mediated signaling.Chronic diseases and translational medicine · 2024Review
- Aberrant Epigenetic Alteration of PAX1 Expression Contributes to Parathyroid Tumorigenesis.The Journal of clinical endocrinology and metabolism · 2022Observational
- Calcium-sensing receptor-mediated NLRP3 inflammasome activation in rheumatoid arthritis and autoinflammation.Frontiers in physiology · 2022Review
- GCM2 Silencing in Parathyroid Adenoma Is Associated With Promoter Hypermethylation and Gain of Methylation on Histone 3.The Journal of clinical endocrinology and metabolism · 2021Article
- Reduced Calcium Sensing Receptor (CaSR) Expression Is Epigenetically Deregulated in Parathyroid Adenomas.The Journal of clinical endocrinology and metabolism · 2020Article
- The CaSR in Pathogenesis of Breast Cancer: A New Target for Early Stage Bone Metastases.Frontiers in oncology · 2020Review
- DNA methylome profiling of granulosa cells reveals altered methylation in genes regulating vital ovarian functions in polycystic ovary syndrome.Clinical epigenetics · 2019Article
- The calcium-sensing receptor in physiology and in calcitropic and noncalcitropic diseases.Nature reviews. Endocrinology · 2018Review
- Calcium-sensing receptor in colorectal inflammation and cancer: Current insights and future perspectives.World journal of gastroenterology · 2018Review
- Article
- Tumor expression of calcium sensing receptor and colorectal cancer survival: Results from the nurses' health study and health professionals follow-up study.International journal of cancer · 2017Article
- Novel FOXG1 mutations in Chinese patients with Rett syndrome or Rett-like mental retardation.BMC medical genetics · 2017Article
- Mediterranean Diet: Prevention of Colorectal Cancer.Frontiers in nutrition · 2017Review
- Calcium-Sensing Receptor Gene: Regulation of Expression.Frontiers in physiology · 2016Review
- Cross Talk between the Calcium-Sensing Receptor and the Vitamin D System in Prevention of Cancer.Frontiers in physiology · 2016Review
- The calcium-sensing receptor: A promising target for prevention of colorectal cancer.Biochimica et biophysica acta · 2015Article
- Persistence of furan-induced epigenetic aberrations in the livers of F344 rats.Toxicological sciences : an official journal of the Society of Toxicology · 2015Article
- The calcium-sensing receptor suppresses epithelial-to-mesenchymal transition and stem cell- like phenotype in the colon.Molecular cancer · 2015Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The calcium-sensing receptor (CaSR) is suggested to mediate the antiproliferative effects of calcium in colon. However, in colorectal cancer (CRC) the expression of the CaSR is silenced and the underlying mechanisms leading to its loss are poorly understood. We investigated whether loss of the CaSR expression in colorectal tumors is caused by DNA hypermethylation and imbalance of transcriptionally permissive/repressive histone alterations. We observed significantly lower CaSR mRNA expression (n = 65, p < 0.001) in colorectal tumors compared with the adjacent mucosa from the same patient. Immunofluorescence staining confirmed downregulation of the CaSR protein also. The CaSR promoter was methylated to a greater extent in tumors compared with adjacent mucosa as determined by bisulfite sequencing (n = 20, p < 0.01) and by pyrosequencing (n = 45, p < 0.001), and methylation correlated inversely with mRNA expression (n = 20, ρ = -0.310, p < 0.05 and n = 45, ρ = -0.588, p < 0.001). Treatments with 5-aza-2'-deoxycytidine (DAC), a DNA methyltransferase inhibitor and/or with two different histone deacetylase inhibitors, trichostatin A (TSA) or suberoylanilide hydroxamic acid (SAHA) restored the expression of CaSR in colon cancer cells. Restored CaSR expression in Coga1A and HT29 cells was functional. Inhibition of lysine-specific demethylase 1 (LSD1) to prevent demethylation of mono- and dimethylated H3K4, increased CaSR expression only marginally. Our data show that hypermethylation of the CaSR promoter and H3K9 deacetylation, but not H3K4me2 demethylation are important factors that cause silencing of the CaSR in colorectal cancer.
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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.