ArticleOncogene2020
Hypoxia-induced release, nuclear translocation, and signaling activity of a DLK1 intracellular fragment in glioma.
Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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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
24 citing papers in PubMed, 38 citations in OpenAlex.
- DLK1 is a GATA1s-driven dependency and therapeutic target in Down syndrome-associated myeloid leukemia.Blood advances · 2026Article
- DLK1: a novel therapeutic target in cancer.Endocrine-related cancer · 2026Review
- Molecular mechanism of Activin receptor inhibition by DLK1.Nature communications · 2025Article
- Coordinated regulation of IGF1R by HIF1α and HIF2α enhances chemoresistance in glioblastoma.Frontiers in pharmacology · 2025Article
- Review
- DLK1 Is Associated with Stemness Phenotype in Medullary Thyroid Carcinoma Cell Lines.International journal of molecular sciences · 2024Article
- Characterization of EpCAM in thyroid cancer biology by three-dimensional spheroids in vitro model.Cancer cell international · 2024Article
- Notch signaling pathway in cancer: from mechanistic insights to targeted therapies.Signal transduction and targeted therapy · 2024Review
- Genome editing and cancer therapy: handling the hypoxia-responsive pathway as a promising strategy.Cellular and molecular life sciences : CMLS · 2023Review
- [Lactate-induced up-regulation of PLEKHA4 promotes proliferation and apoptosis of human glioma cells].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2023Article
- Review
- Pituitary Tumor-Transforming Gene 1/Delta like Non-Canonical Notch Ligand 1 Signaling in Chronic Liver Diseases.International journal of molecular sciences · 2022Review
- Molecular Mechanisms and Clinical Challenges of Glioma Invasion.Brain sciences · 2022Review
- Topographic mapping of the glioblastoma proteome reveals a triple-axis model of intra-tumoral heterogeneity.Nature communications · 2022Article
- Small Interfering RNA for Gliomas Treatment: Overcoming Hurdles in Delivery.Frontiers in cell and developmental biology · 2022Review
- Emerging Roles of DLK1 in the Stem Cell Niche and Cancer Stemness.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2022Review
- YTHDC1-mediated VPS25 regulates cell cycle by targeting JAK-STAT signaling in human glioma cells.Cancer cell international · 2021Article
- HAX1 maintains the glioma progression in hypoxia through promoting mitochondrial fission.Journal of cellular and molecular medicine · 2021Article
- Investigation of the Effects and Mechanisms of Anticancer Action of a Ru(II)-Arene Iminophosphorane Compound in Triple Negative Breast Cancer Cells.ChemMedChem · 2021Article
- Thyroid Cancer Stem-Like Cells: From Microenvironmental Niches to Therapeutic Strategies.Journal of clinical medicine · 2021Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glioblastoma multiforme is characterized in part by severe hypoxia associated with tumor necrosis. The cellular response to hypoxia can influence several properties of tumor cells associated with aggressive tumor growth, including metabolic adaptations and tumor cell migration and invasion. Here, we found that Delta Like Non-Canonical Notch Ligand 1 (DLK1) expression was elevated as compared with normal brain in a genetically engineered mouse model of glioma, and that DLK1 expression increased with tumor grade in human glioma samples. DLK1 expression was highest in hypoxic and perivascular tumor areas, and we found that hypoxia induced the release and nuclear translocation of an intracellular fragment of DLK1 in murine glioma as well as in human glioma cultures. Release of the intracellular fragment was dependent on ADAM17 and Hypoxia-inducible Factor 1alpha and 2alpha (HIF-1alpha/HIF-2alpha), as ADAM17 inhibitors and HIF1A/HIF2A siRNA blocked DLK1 cleavage. Expression of a cleavable form of DLK1 amplified several hypoxia-induced traits of glioma cells such as colony formation, stem cell marker gene expression, a PI3K-pathway-mediated metabolic shift, and enhanced invasiveness. Effects of DLK1 were dependent on DLK1-cleavage by ADAM17, as expression of non-cleavable DLK1 could not replicate the DLK1-induced hypoxic phenotype. Finally, forced expression of DLK1 resulted in more invasive tumor growth in a PDGFB-induced glioma mouse model without affecting overall survival. Together, our findings suggest a previously undescribed role for DLK1 as an intracellular signaling molecule.
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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.