ArticleBMC cancer2019
Hypoxia-induced cancer stemness acquisition is associated with CXCR4 activation by its aberrant promoter demethylation.
Article in BMC cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 37 citations in OpenAlex.
- Regulatory T cells in hypoxic environments.Frontiers in immunology · 2026Review
- Stemness-hypoxia genesTranslational cancer research · 2025Article
- Investigating combined hypoxia and stemness indices for prognostic transcripts in gastric cancer: Machine learning and network analysis approaches.Biochemistry and biophysics reports · 2025Article
- Identification and Characterization of Oxidative Stress and Endoplasmic Reticulum Stress-Related Genes in Esophageal Cancer.Journal of Cancer · 2025Article
- Cancer stem cells: advances in knowledge and implications for cancer therapy.Signal transduction and targeted therapy · 2024Review
- Demethylation in promoter region of severely damaged hepatocytes enhances chemokine receptor CXCR4 gene expression.Histochemistry and cell biology · 2023Article
- Revisiting Epithelial Carcinogenesis.International journal of molecular sciences · 2022Article
- 5-Aminolevulinic acid overcomes hypoxia-induced radiation resistance by enhancing mitochondrial reactive oxygen species production in prostate cancer cells.British journal of cancer · 2022Article
- Long-Term Hypoxia Maintains a State of Dedifferentiation and Enhanced Stemness in Fetal Cardiovascular Progenitor Cells.International journal of molecular sciences · 2021Article
- Review
- Lessons from the Embryo: an Unrejected Transplant and a Benign Tumor.Stem cell reviews and reports · 2021Review
- Cephalomannine inhibits hypoxia-induced cellular function via the suppression of APEX1/HIF-1α interaction in lung cancer.Cell death & disease · 2021Article
- Review
- The role of hypoxia in the tumor microenvironment and development of cancer stem cell: a novel approach to developing treatment.Cancer cell international · 2021Review
- The Effect of Hypoxia on the Expression of CXC Chemokines and CXC Chemokine Receptors-A Review of Literature.International journal of molecular sciences · 2021Review
- Review
- Emerging data supporting stromal cell therapeutic potential in cancer: reprogramming stromal cells of the tumor microenvironment for anti-cancer effects.Cancer biology & medicine · 2020Review
- CXCR4Respiratory research · 2020Article
- TGF-β induced EMT and stemness characteristics are associated with epigenetic regulation in lung cancer.Scientific reports · 2020Article
- Epigenetics and metabolism at the crossroads of stress-induced plasticity, stemness and therapeutic resistance in cancer.Theranostics · 2020Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundA hypoxic microenvironment leads to an increase in the invasiveness and the metastatic potential of cancer cells within tumors via the epithelial-mesenchymal transition (EMT) and cancer stemness acquisition. However, hypoxia-induced changes in the expression and function of candidate stem cell markers and their possible molecular mechanism is still not understood.
methodsLung cell lines were analyzed in normoxic or hypoxic conditions. For screening among the stem cell markers, a transcriptome analysis using next-generation sequencing was performed. For validation, the EMT and stem cell characteristics were analyzed. To determine whether an epigenetic mechanism was involved, the cell lines were treated with a DNA methyltransferase inhibitor (AZA), and methylation-specific PCR and bisulfite sequencing were performed.
resultsNext-generation sequencing revealed that the CXCR4 expression was significantly higher after the hypoxic condition, which functionally resulted in the EMT and cancer stemness acquisition. The acquisition of the EMT and stemness properties was inhibited by treatment with CXCR4 siRNA. The CXCR4 was activated by either the hypoxic condition or treatment with AZA. The methylation-specific PCR and bisulfite sequencing displayed a decreased CXCR4 promoter methylation in the hypoxic condition.
conclusionsThese results suggest that hypoxia-induced acquisition of cancer stem cell characteristics was associated with CXCR4 activation by its aberrant promoter demethylation.
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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.