ArticleOncogene2018
Astrocyte-derived CCL20 reinforces HIF-1-mediated hypoxic responses in glioblastoma by stimulating the CCR6-NF-κB signaling pathway.
Article in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 61 citations in OpenAlex.
- Advances in the role of astrocytes in glioma progression and therapy.Acta pharmacologica Sinica · 2026Review
- Advances in hypoxia-modulated blood oxygen level-dependent MRI: a narrative review of physiological principles and applications for glioblastoma imaging.Magma (New York, N.Y.) · 2026Review
- The intersection of chemokine signaling with the hallmarks of cancer in glioblastoma.Journal of neuro-oncology · 2026Review
- Article
- CCL20-CCR6 axis in autoimmune disease and cancer progression: clinical and therapeutic implications.Cell communication and signaling : CCS · 2026Review
- Radiation-activated astrocytes promote tumor progression through CXCL12 secretion and induce resistance to anti-PD-1 immunotherapy.Translational cancer research · 2026Article
- KITENIN-CCL20 axis is a potential therapeutic target for modulating immunosuppressive tumor microenvironment in glioblastoma.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Epitranscriptomic control of epithelial-mesenchymal transition in cancer: mechanisms, plasticity, and therapeutic opportunities.Frontiers in cell and developmental biology · 2026Review
- Transcriptomic landscape of human circular RNAs: unveiling molecular mechanisms in high-altitude adaptation.Frontiers in genetics · 2026Article
- Inhibitory effect of Endostar on HIF-1 with upregulation of MHC-I in lung cancer cells.Cancer biology & therapy · 2025Article
- CCL20 in the tumor microenvironment: implications for cancer progression and therapeutic approaches.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- LncRNAs in hypoxic microenvironment; insight in their impact in cancer biology.Functional & integrative genomics · 2025Review
- Breaking Down Glioma-Microenvironment Crosstalk.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2025Review
- Reactive Astrocytes in Glioma: Emerging Opportunities and Challenges.International journal of molecular sciences · 2025Review
- Deciphering the topological landscape of glioma using a network theory framework.Scientific reports · 2024Article
- The role of IL-17 in the pathogenesis and treatment of glioblastoma-an update on the state of the art and future perspectives.Medical oncology (Northwood, London, England) · 2024Review
- RANKL/RANK signaling recruits Tregs via the CCL20-CCR6 pathway and promotes stemness and metastasis in colorectal cancer.Cell death & disease · 2024Article
- Review
- TH1L involvement in colorectal cancer pathogenesis by regulation of CCL20 through the NF-κB signalling pathway.Journal of cellular and molecular medicine · 2024Article
- Biosensor-Enhanced Organ-on-a-Chip Models for Investigating Glioblastoma Tumor Microenvironment Dynamics.Sensors (Basel, Switzerland) · 2024Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During tumor development, stromal cells are co-opted to the tumor milieu and provide favorable conditions for the tumor. Hypoxia stimulates cancer cells to acquire a more malignant phenotype via activation of hypoxia-inducible factor 1 (HIF-1). Given that cancer cells and astrocytes in glioblastomas coexist in a hypoxic microenvironment, we examined whether astrocytes affect the adaptation of glioblastoma cells to hypoxia. Immunoblotting, reporter assays, quantitative RT-PCR, and chromatin immunoprecipitation were performed to evaluate HIF-1 signaling in glioblastoma cells. Astrocyte-derived chemokine C-C motif ligand 20 (CCL20) was identified using cytokine arrays, and its role in glioblastoma development was evaluated in orthotopic xenografts. Astrocytes augmented HIF-1α expression in glioblastoma cells under hypoxia. The expression of HIF-1 downstream genes, cancer colony formation, and Matrigel invasion of glioblastoma cells were stimulated by conditioned medium from astrocytes pre-exposed to hypoxia. CCL20 was secreted in a hypoxia-dependent manner from astrocytes and busted the hypoxic induction of HIF-1α in glioblastoma cells. Mechanistically, the CCL20/CCR6 signaling pathway upregulates HIF-1α by stimulating nuclear factor kappa B-driven transactivation of the HIF1A gene. Compared with the control tumors, CCR6-deficient glioblastoma xenografts grew more slowly, with poor vascularization, and expressed lower levels of HIF-1α and its downstream proteins. Furthermore, CCR6 expression was correlated with HIF-1α expression in GEO and TCGA datasets from human glioblastoma tissues. These results suggest that glioblastoma cells adapt well to hypoxic stress by virtue of CCL20 derived from neighboring astrocytes.
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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.