ArticleThe Journal of biological chemistry2016
Simultaneous Activation of Induced Heterodimerization between CXCR4 Chemokine Receptor and Cannabinoid Receptor 2 (CB2) Reveals a Mechanism for Regulation of Tumor Progression.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
62 citing papers in PubMed, 2 syntheses or guidelines pooled it, 94 citations in OpenAlex.
- Cannabinoid Receptors: An Update on Cell Signaling, Pathophysiological Roles and Therapeutic Opportunities in Neurological, Cardiovascular, and Inflammatory Diseases.International journal of molecular sciences · 2020Pooled it
- Cannabinoids and Prostate Cancer: A Systematic Review of Animal Studies.International journal of molecular sciences · 2020Pooled it
- Cannabis in cancer: a review of therapeutic potential, clinical and preclinical status, and legislation.Archives of pharmacal research · 2026Review
- Pharmacological modulation of CXCL12/CXCR4/ACKR3 for brain disorders - an overview.Cell communication and signaling : CCS · 2026Review
- The relevance of cannabinoid receptor 2 in the central nervous system: an update over the last 3 years.Frontiers in behavioral neuroscience · 2026Review
- In Vitro Signaling Properties of Cannabinoid and Orexin Receptors: How Orexin Receptors Influence Cannabinoid Receptor-Mediated Signaling.Pharmacology research & perspectives · 2025Article
- The Use of Biologics for Targeting GPCRs in Metastatic Cancers.Biotech (Basel (Switzerland)) · 2025Review
- G protein-coupled receptors in prostate cancer: research progress and therapeutic targets.Frontiers in cell and developmental biology · 2025Review
- Foxq1 activates CB2R with oleamide to alleviate POCD.Brain pathology (Zurich, Switzerland) · 2025Article
- Involvement of CXCL12/CXCR4 in CB2 receptor agonist-attenuated morphine tolerance in Walker 256 tumor-bearing rats with cancer pain.European journal of medical research · 2024Article
- The β2-adrenergic receptor associates with CXCR4 multimers in human cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Computational Characterization of Membrane Proteins as Anticancer Targets: Current Challenges and Opportunities.International journal of molecular sciences · 2024Review
- LPA1-mediated inhibition of CXCR4 attenuates CXCL12-induced signaling and cell migration.Cell communication and signaling : CCS · 2023Article
- G protein activation via chemokine (C-X-C motif) receptor 4 and αFEBS letters · 2023Article
- The Role of Cannabinoids in CNS Development: Focus on Proliferation and Cell Death.Cellular and molecular neurobiology · 2023Review
- 2-Arachidonoylglycerol Modulates CXCL12-Mediated Chemotaxis in Mantle Cell Lymphoma and Chronic Lymphocytic Leukemia.Cancers · 2023Article
- Identification of Novel CB2 Ligands through Virtual Screening and In Vitro Evaluation.Journal of chemical information and modeling · 2023Article
- Simultaneous activation of CXC chemokine receptor 4 and histamine receptor H1 enhances calcium signaling and cancer cell migration.Scientific reports · 2023Article
- Should oncologists trust cannabinoids?Frontiers in pharmacology · 2023Review
- Cannabinoids as anticancer drugs: current status of preclinical research.British journal of cancer · 2022Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
The G-protein-coupled chemokine receptor CXCR4 generates signals that lead to cell migration, cell proliferation, and other survival mechanisms that result in the metastatic spread of primary tumor cells to distal organs. Numerous studies have demonstrated that CXCR4 can form homodimers or can heterodimerize with other G-protein-coupled receptors to form receptor complexes that can amplify or decrease the signaling capacity of each individual receptor. Using biophysical and biochemical approaches, we found that CXCR4 can form an induced heterodimer with cannabinoid receptor 2 (CB2) in human breast and prostate cancer cells. Simultaneous, agonist-dependent activation of CXCR4 and CB2 resulted in reduced CXCR4-mediated expression of phosphorylated ERK1/2 and ultimately reduced cancer cell functions such as calcium mobilization and cellular chemotaxis. Given that treatment with cannabinoids has been shown to reduce invasiveness of cancer cells as well as CXCR4-mediated migration of immune cells, it is plausible that CXCR4 signaling can be silenced through a physical heterodimeric association with CB2, thereby inhibiting subsequent functions of CXCR4. Taken together, the data illustrate a mechanism by which the cannabinoid system can negatively modulate CXCR4 receptor function and perhaps tumor progression.
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What OpenQuestion holds
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.