ArticleActa neuropathologica communications2019
Epigenetic downregulation of STAT6 increases HIF-1α expression via mTOR/S6K/S6, leading to enhanced hypoxic viability of glioma cells.
Article in Acta neuropathologica communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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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.
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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
11 citing papers in PubMed, 21 citations in OpenAlex.
- SOX4-STAT6-MTHFD2 axis drives hepatocellular carcinoma progression and treatment resistance.Cell death & disease · 2026Article
- Emerging Therapeutic Targets in Rheumatoid Arthritis: Focusing on HIF-1α, Nrf2, STATs, and RORγt.Current drug targets · 2025Review
- The lactate metabolism and protein lactylation in epilepsy.Frontiers in cellular neuroscience · 2024Review
- STAT6 in mitochondrial outer membrane impairs mitochondrial fusion by inhibiting MFN2 dimerization.iScience · 2022Article
- Review
- Review
- Doxorubicin induced immune abnormalities and inflammatory responses via HMGB1, HIF1-α and VEGF pathway in progressive of cardiovascular damage.Annals of medicine and surgery (2012) · 2022Review
- STAT6 Upregulates NRP1 Expression in Endothelial Cells and Promotes Angiogenesis.Frontiers in oncology · 2022Article
- Hypoxia Enhances HIF1Stem cells international · 2022Article
- Influence of CeInternational journal of molecular sciences · 2021Article
- Interleukin 4 Affects Epilepsy by Regulating Glial Cells: Potential and Possible Mechanism.Frontiers in molecular neuroscience · 2020Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Multifunctional signal transducer and activator of transcription (STAT) proteins play important roles in cancer. Here, we have shown that STAT6 is epigenetically silenced in some cases of malignant glioblastoma, which facilitates cancer cell survival in a hypoxic microenvironment. This downregulation results from hypermethylation of CpG islands within the STAT6 promoter by DNA methyltransferases. STAT6 interacts with Rheb under hypoxia and inhibits mTOR/S6K/S6 signaling, in turn, inducing increased HIF-1α translation. STAT6 silencing and consequent tumor-promoting effects are additionally observed in glioma stem-like cells (GSC). Despite recent advances in cancer treatment, survival rates have shown little improvement. This is particularly true in the case of glioma, where multimodal treatment and precision medicine is needed. Our study supports the application of epigenetic restoration of STAT6 with the aid of DNA methyltransferase inhibitors, such as 5-aza-2-deoxycytidine, for treatment of STAT6-silenced gliomas.
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Registered trials
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