ArticleBiology open2012
TLX controls angiogenesis through interaction with the von Hippel-Lindau protein.
Article in Biology open, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed, 22 citations in OpenAlex.
- Advanced Biomaterial Delivery of Hypoxia-Conditioned Extracellular Vesicles (EVs) as a Therapeutic Platform for Traumatic Brain Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Single-cell analysis reveals inflammatory interactions driving macular degeneration.Nature communications · 2023Article
- Tailless and hypoxia inducible factor-2α cooperate to sustain proangiogenic states of retinal astrocytes in neonatal mice.Biology open · 2023Article
- TLX, an Orphan Nuclear Receptor With Emerging Roles in Physiology and Disease.Endocrinology · 2021Review
- Tumorigenic effects of TLX overexpression in HEK 293T cells.Cancer reports (Hoboken, N.J.) · 2019Article
- Computer-Aided Discovery of Small Molecule Inhibitors of Transcriptional Activity of TLX (NR2E1) Nuclear Receptor.Molecules (Basel, Switzerland) · 2018Article
- TLX-Its Emerging Role for Neurogenesis in Health and Disease.Molecular neurobiology · 2017Review
- The Orphan Nuclear Receptor TLX/NR2E1 in Neural Stem Cells and Diseases.Neuroscience bulletin · 2016Review
- Expression profiling of nuclear receptors in breast cancer identifies TLX as a mediator of growth and invasion in triple-negative breast cancer.Oncotarget · 2015Article
- TLX activates MMP-2, promotes self-renewal of tumor spheres in neuroblastoma and correlates with poor patient survival.Cell death & disease · 2014Article
- Minireview: role of orphan nuclear receptors in cancer and potential as drug targets.Molecular endocrinology (Baltimore, Md.) · 2014Review
- Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TLX is known as the orphan nuclear receptor indispensable for maintaining neural stem cells in adult neurogenesis. We report here that neuroblastoma cell lines express high levels of TLX, which further increase in hypoxia to enhance the angiogenic capacity of these cells. The proangiogenetic activity of TLX appears to be induced by its direct binding to the von Hippel-Lindau protein (pVHL), which stabilizes TLX. In turn, TLX competes with hydroxylated hypoxia-inducible factor (HIF-α) for binding to pVHL, which contributes to the stabilization of HIF-2α in neuroblastoma during normoxia. Upon hypoxia, TLX increases in the nucleus where it binds in close proximity of the HIF-response element on the VEGF-promoter chromatin, and, together with HIF-2α, recruits RNA polymerase II to induce VEGF expression. Conversely, depletion of TLX by shRNA decreases the expression of HIF-2α and VEGF as well as the growth-promoting and colony-forming capacity of the neuroblastoma cell lines IMR-32 and SH-SY5Y. On the contrary, silencing HIF-2α will slightly increase TLX, suggesting that TLX acts to maintain a hypoxic environment when HIF-2α is decreasing. Our results demonstrate TLX to play a key role in controlling angiogenesis by regulating HIF-2α. TLX and pVHL might counterbalance each other in important fate decisions such as self-renewal and differentiation, as well as angiogenesis and anti-angiogenesis.
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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.