ArticleProceedings of the National Academy of Sciences of the United States of America2018
Hypoxia-inducible factor 1-dependent expression of adenosine receptor 2B promotes breast cancer stem cell enrichment.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT04976660 (Phase I/II First-in-Human Study of TT-4 As a Single Agent in Participants with Advanced Selected Solid Tumors), which is not on this map. Cited by 88 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.
The trial behind it
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.
Phase I/II First-in-Human Study of TT-4 As a Single Agent in Participants with Advanced Selected Solid Tumors
Who cites it
88 citing papers in PubMed, 130 citations in OpenAlex.
- Adenosine A2B Receptor Promotes Tumor Progression and Metastases in Undifferentiated Pleomorphic Sarcoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Adenosine signaling in tumor immune escape: metabolic checkpoints, myeloid suppression, and combination immunotherapy.Frontiers in oncology · 2026Review
- AMarine drugs · 2025Article
- SETD7 exacerbates diabetic nephropathy through activating ACell & bioscience · 2025Article
- Anticancer Activity of Triterpene Glycosides Cucumarioside AInternational journal of molecular sciences · 2025Article
- FTO activates PD-L1 promotes immunosuppression in breast cancer via the m6A/YTHDF3/PDK1 axis under hypoxic conditions.Journal of advanced research · 2025Article
- Extracellular Adenosine in Gastric Cancer: The Role of GCSCs.International journal of molecular sciences · 2025Article
- Purinergic pathways and their clinical use in the treatment of acute myeloid leukemia.Purinergic signalling · 2025Review
- The progress and prospects of targeting the adenosine pathway in cancer immunotherapy.Biomarker research · 2025Review
- A novel L-shaped ortho-quinone analog targeting adenosine A2b receptor to inhibit epithelial-mesenchymal transition in colorectal cancer cells.Medical oncology (Northwood, London, England) · 2025Article
- Purinergic system in cancer stem cells.Purinergic signalling · 2025Review
- Article
- The Role of Adenosine in Overcoming Resistance in Sarcomas.International journal of molecular sciences · 2024Review
- Environmental purines decrease Pseudomonas aeruginosa biofilm formation by disrupting c-di-GMP metabolism.Cell reports · 2024Article
- Tumor microenvironment of cancer stem cells: Perspectives on cancer stem cell targeting.Genes & diseases · 2024Review
- Adenosine receptors in breast cancer.Molecular biology reports · 2024Review
- Superbinder based phosphoproteomic landscape revealed PRKCD_pY313 mediates the activation of Src and p38 MAPK to promote TNBC progression.Cell communication and signaling : CCS · 2024Article
- Dielectrophoretic enrichment of live chemo-resistant circulating-like pancreatic cancer cells from media of drug-treated adherent cultures of solid tumors.Lab on a chip · 2024Article
- Hypoxia-inducible factor in breast cancer: role and target for breast cancer treatment.Frontiers in immunology · 2024Review
- Exploratory Research for HIF-1α Overexpression Tumor Antigen in the Activation of Dendritic Cells and the Potent Anti-Tumor Immune Response.Cancer management and research · 2024Article
28 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Breast cancer stem cells (BCSCs), which are characterized by a capacity for unlimited self-renewal and for generation of the bulk cancer cell population, play a critical role in cancer relapse and metastasis. Hypoxia is a common feature of the cancer microenvironment that stimulates the specification and maintenance of BCSCs. In this study, we found that hypoxia increased expression of adenosine receptor 2B (A2BR) in human breast cancer cells through the transcriptional activity of hypoxia-inducible factor 1. The binding of adenosine to A2BR promoted BCSC enrichment by activating protein kinase C-δ, which phosphorylated and activated the transcription factor STAT3, leading to increased expression of interleukin 6 and NANOG, two key mediators of the BCSC phenotype. Genetic or pharmacological inhibition of A2BR expression or activity decreased hypoxia- or adenosine-induced BCSC enrichment in vitro, and dramatically impaired tumor initiation and lung metastasis after implantation of MDA-MB-231 human breast cancer cells into the mammary fat pad of immunodeficient mice. These data provide evidence that targeting A2BR might be an effective strategy to eradicate BCSCs.
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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.