ArticleCell cycle (Georgetown, Tex.)2012
Estrogen receptor α is a novel target of the Von Hippel-Lindau protein and is responsible for the proliferation of VHL-deficient cells under hypoxic conditions.
Article in Cell cycle (Georgetown, Tex.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Is hysterectomy associated with kidney cancer risk? A meta-analysis of cohort studies.Frontiers in oncology · 2023Pooled it
- The Role of Estrogen Signaling Pathway and Targeted Therapy Exploration in Urological Tumors.International journal of biological sciences · 2026Review
- Regional and Sexual Dimorphism in Murine Skeletal Responses to Osteocytic HIF Pathway Modulation.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2026Article
- The influence of sex hormones on renal cell carcinoma.Therapeutic advances in medical oncology · 2024Review
- Critical role of VHL/BICD2/STAT1 axis in crystal-associated kidney disease.Cell death & disease · 2023Article
- Hypoxia and ERα Transcriptional Crosstalk Is Associated with Endocrine Resistance in Breast Cancer.Cancers · 2022Article
- Review
- Role of the androgen, estrogen, and progesterone receptors in adherent perinephric fat in robotic partial nephrectomy.Journal of robotic surgery · 2022Article
- VHL syndrome without clear family history: A rare case report and literature review of Chinese patients.Frontiers in neurology · 2022Article
- Review
- Cardiovascular Risk After SARS-CoV-2 Infection Is Mediated by IL18/IL18R1/HIF-1 Signaling Pathway Axis.Frontiers in immunology · 2021Article
- TET is targeted for proteasomal degradation by the PHD-pVHL pathway to reduce DNA hydroxymethylation.The Journal of biological chemistry · 2020Article
- Hypoxia differentially regulates estrogen receptor alpha in 2D and 3D culture formats.Archives of biochemistry and biophysics · 2019Article
- Genome-independent hypoxic repression of estrogen receptor alpha in breast cancer cells.BMC cancer · 2017Article
- Oestrogen receptor negativity in breast cancer: a cause or consequence?Bioscience reports · 2016Review
- WSB1 promotes tumor metastasis by inducing pVHL degradation.Genes & development · 2015Article
- Distinct breast cancer stem/progenitor cell populations require either HIF1α or loss of PHD3 to expand under hypoxic conditions.Oncotarget · 2015Article
- High ERα36 Expression Level and Membrane Location Predict Poor Prognosis in Renal Cell Carcinoma.Medicine · 2015Observational
- Ubiquitylation of nuclear receptors: new linkages and therapeutic implications.Journal of molecular endocrinology · 2015Review
- VHL negatively regulates SARS coronavirus replication by modulating nsp16 ubiquitination and stability.Biochemical and biophysical research communications · 2015Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Von Hippel-Lindau gene (VHL) is frequently deleted or mutated in human renal cell carcinoma (RCC) at the early stage. According to the well-established theory, pVHL acts as a tumor suppressor through its E3 ligase activity, which targets hypoxia-inducing factor-1α (HIF-1α). However, the elevated expression of HIF-1α did not promote cell proliferation, indicating that there would be another target, which could promote cell proliferation at the early cancer stage of RCC. In this study, we show that estrogen receptor-α (ER-α) is a novel proteasomal degradation target of the pVHL E3 ligase. Indeed, the overexpression of VHL suppresses exo- and endogenous ER-α expression, whereas si-pVHL can increase ER-α expression. The negative regulation of pVHL on ER-α expression is achieved by its E3 ligase activity. Thus, pVHL can promote the ER-α ubiquitinylation. In addition, we revealed that ER-α and HIF-1α are competitive substrates of pVHL. Thus, under normal conditions, ER-α overexpression can increase the transcription factor activity of HIF-1α. Under the hypoxic condition, where HIF-1α is not a suitable target of pVHL, ER-α is more rapidly degraded by pVHL. However, in VHL-deficient cells, the expression of ER-α and HIF-1α is retained, so that the hypoxic condition did not suppress cell proliferation obviously compared with cells that are expressing pVHL. Thus, blocking of ER-α using its inhibitor could suppress the proliferation of VHL-deficient cells as effectively as hypoxia-induced growth suppression. Considering our results, blocking of ER-α signaling in VHL-deficient cancer cells would be beneficial for cancer suppression. Indeed, we showed the anti-proliferative effect of Faslodex in VHL-deficient cells.
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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.