ArticleThe EMBO journal2024
Nuclear receptor E75/NR1D2 promotes tumor malignant transformation by integrating Hippo and Notch pathways.
Article in The EMBO journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Cross-species insights from ART-D to uncover evolutionarily conserved oncogenic mechanisms.Molecular systems biology · 2026Article
- Article
- Mechanism of matrine inhibiting retinoblastoma cell growth by downregulating NR1D2 to regulate phosphorylation of the PI3K/AKT signaling pathway.Scientific reports · 2026Article
- [KLF10 overexpression alleviates neuroinflammation and anxiety-depressive disorder in rats by downregulating the NF-κB/NLRP3 pathway].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- Mitochondrial gatekeeper in hepatocellular carcinoma: Unraveling the multifaceted roles of VDAC in metabolic reprogramming, apoptosis evasion and therapeutic innovation (Review).Molecular medicine reports · 2026Review
- Circadian clock and cancer.Military Medical Research · 2026Review
- Regulation of Stemness by NR1D2 in Colorectal Cancer.Biomedicines · 2025Article
- Nuclear receptors as novel regulators that modulate cancer radiosensitivity and normal tissue radiotoxicity.Molecular cancer · 2025Review
- Developmental exposure of antibiotics shortens life span and induces teratogenicity inToxicology reports · 2024Article
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Authors and funding
12 authors.
Funding
Abstract
Hormone therapy resistance and the ensuing aggressive tumor progression present a significant clinical challenge. However, the mechanisms underlying the induction of tumor malignancy upon inhibition of steroid hormone signaling remain poorly understood. Here, we demonstrate that Drosophila malignant epithelial tumors show a similar reduction in ecdysone signaling, the main steroid hormone pathway. Our analysis of ecdysone-induced downstream targets reveals that overexpression of the nuclear receptor E75, particularly facilitates the malignant transformation of benign tumors. Genome-wide DNA binding profiles and biochemistry data reveal that E75 not only binds to the transcription factors of both Hippo and Notch pathways, but also exhibits widespread co-binding to their target genes, thus contributing to tumor malignancy. We further validated these findings by demonstrating that depletion of NR1D2, the mammalian homolog of E75, inhibits the activation of Hippo and Notch target genes, impeding glioblastoma progression. Together, our study unveils a novel mechanism by which hormone inhibition promotes tumor malignancy, and describes an evolutionarily conserved role of the oncogene E75/NR1D2 in integration of Hippo and Notch pathway activity during tumor progression.
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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.