The ERRα–VDR axis promotes calcitriol degradation and estrogen signaling in breast cancer cells, while VDR‐CYP24A1‐ERRα overexpression correlates with poor prognosis in patients with basal‐like breast cancer
| العنوان: | The ERRα–VDR axis promotes calcitriol degradation and estrogen signaling in breast cancer cells, while VDR‐CYP24A1‐ERRα overexpression correlates with poor prognosis in patients with basal‐like breast cancer |
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| المؤلفون: | Stefania Tommasi, Letizia Porcelli, Roberta Di Fonte, Simona De Summa, Rosanna Lacalamita, Amalia Azzariti, Brunella Pilato, Katia Danza, Simona Serratì |
| المصدر: | Molecular Oncology, Vol 16, Iss 4, Pp 904-920 (2022) |
| بيانات النشر: | Wiley, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | calcitriol, Cancer Research, Calcitriol, Breast Neoplasms, Calcitriol receptor, Transactivation, Cyclin D1, breast cancer, Coactivator, Genetics, medicine, polycyclic compounds, Humans, Aromatase, Vitamin D3 24-Hydroxylase, RC254-282, VDR, biology, ERRα, Cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Estrogens, General Medicine, medicine.disease, CYP24A1, Receptors, Estrogen, Oncology, Cancer research, biology.protein, Receptors, Calcitriol, Molecular Medicine, Female, lipids (amino acids, peptides, and proteins), Co-Repressor Proteins, Estrogen receptor alpha, Transcription Factors, medicine.drug |
| الوصف: | Vitamin D is used to reduce cancer risk and improve the outcome of cancer patients, but the vitamin D receptor (VDR; also known as the calcitriol receptor) pathway needs to be functionally intact to ensure the biological effects of circulating calcitriol, the active form of vitamin D. Besides estrogen receptor alpha (ERα), estrogen-related receptor alpha (ERRα) has also been shown to interfere with the VDR pathway, but its role in the antitumor and transactivation activity of calcitriol is completely unknown in breast cancer (BC). We observed that ERRα functionally supported the proliferation of BC cell lines and acted as a calcitriol-induced regulator of VDR. As such, ERRα deregulated the calcitriol-VDR transcription by enhancing the expression of CYP24A1 as well as of both ERα and aromatase (CYP19A1) in calcitriol-treated cells. ERRα knockdown limited the effect of calcitriol by reducing calcitriol-induced G0/G1 phase cell cycle arrest and by affecting the expression of cyclin D1 and p21/Waf. The interactome analysis suggested that Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-α (PGC-1α) and Proline-, glutamic acid-, and leucine-rich protein 1 (PELP-1) are key players in the genomic actions of the calcitriol-VDR-ERRα axis. Evaluation of patient outcomes in the The Cancer Genome Atlas (TCGA) dataset showed the translational significance of the biological effects of the VDR-ERRα axis, highlighting that VDR, CYP24A1 and ERRα overexpression correlates with poor prognosis in basal-like BC. |
| اللغة: | English |
| تدمد: | 1574-7891 1878-0261 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a0270105893f0c4c0a2ef143b21ce0e3Test https://doaj.org/article/4a3c78e8a74c4d76a4b251811673088bTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a0270105893f0c4c0a2ef143b21ce0e3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15747891 18780261 |
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