ArticleScience signaling2013
An adenosine-mediated signaling pathway suppresses prenylation of the GTPase Rap1B and promotes cell scattering.
Article in Science signaling, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 86 citations in OpenAlex.
- Rap1A, Rap1B, and β-Adrenergic Signaling in Autologous HCT: A Randomized Controlled Trial of Propranolol.The Yale journal of biology and medicine · 2022Trial
- Divergent Functions of Rap1A and Rap1B in Endothelial Biology and Disease.International journal of molecular sciences · 2025Review
- Protein lipidation in the tumor microenvironment: enzymology, signaling pathways, and therapeutics.Molecular cancer · 2025Review
- Towards Targeting Endothelial Rap1B to Overcome Vascular Immunosuppression in Cancer.International journal of molecular sciences · 2024Review
- Current Understanding of the Role of Adenosine Receptors in Cancer.Molecules (Basel, Switzerland) · 2024Review
- Istradefylline modulates purinergic enzymes and reduces malignancy-associated factors in B16F10 melanoma cells.Purinergic signalling · 2023Article
- Host Cell Rap1b mediates cAMP-dependent invasion by Trypanosoma cruzi.PLoS neglected tropical diseases · 2023Article
- The adenosinergic machinery in cancer: In-tandem insights from basic mechanisms to therapy.Frontiers in immunology · 2023Review
- Avian Hepatitis E Virus ORF2 Protein Interacts with Rap1b to Induce Cytoskeleton Rearrangement That Facilitates Virus Internalization.Microbiology spectrum · 2022Article
- Current Adenosinergic Therapies: What Do Cancer Cells Stand to Gain and Lose?International journal of molecular sciences · 2021Review
- Molecular and Pharmacological Characterization of the Interaction between Human Geranylgeranyltransferase Type I and Ras-Related Protein Rap1B.International journal of molecular sciences · 2021Article
- Identification of a subset of immunosuppressive P2RX1-negative neutrophils in pancreatic cancer liver metastasis.Nature communications · 2021Article
- SmgGDS: An Emerging Master Regulator of Prenylation and Trafficking by Small GTPases in the Ras and Rho Families.Frontiers in molecular biosciences · 2021Review
- Purinergic Signaling in Pancreas-From Physiology to Therapeutic Strategies in Pancreatic Cancer.International journal of molecular sciences · 2020Review
- Study and analysis of antitumor resistance mechanism of PD1/PD-L1 immune checkpoint blocker.Cancer medicine · 2020Review
- The adenosine pathway in immuno-oncology.Nature reviews. Clinical oncology · 2020Review
- Long noncoding RNA LINC00514 accelerates pancreatic cancer progression by acting as a ceRNA of miR-28-5p to upregulate Rap1b expression.Journal of experimental & clinical cancer research : CR · 2020Article
- The Expression of Adenosine A2B Receptor on Antigen-Presenting Cells Suppresses CD8Cancer immunology research · 2020Article
- Integration of Rap1 and Calcium Signaling.International journal of molecular sciences · 2020Review
- Splice switching an oncogenic ratio of SmgGDS isoforms as a strategy to diminish malignancy.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
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10 authors at 1 institution in 1 country.
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Abstract
During metastasis, cancer cells acquire the ability to dissociate from each other and migrate, which is recapitulated in vitro as cell scattering. The small guanosine triphosphatase (GTPase) Rap1 opposes cell scattering by promoting cell-cell adhesion, a function that requires its prenylation, or posttranslational modification with a carboxyl-terminal isoprenoid moiety, to enable its localization at cell membranes. Thus, signaling cascades that regulate the prenylation of Rap1 offer a mechanism to control the membrane localization of Rap1. We identified a signaling cascade initiated by adenosine A2B receptors that suppressed the prenylation of Rap1B through phosphorylation of Rap1B, which decreased its interaction with the chaperone protein SmgGDS (small GTPase guanosine diphosphate dissociation stimulator). These events promoted the cytosolic and nuclear accumulation of nonprenylated Rap1B and diminished cell-cell adhesion, resulting in cell scattering. We found that nonprenylated Rap1 was more abundant in mammary tumors than in normal mammary tissue in rats and that activation of adenosine receptors delayed Rap1B prenylation in breast, lung, and pancreatic cancer cell lines. Our findings support a model in which high concentrations of extracellular adenosine, such as those that arise in the tumor microenvironment, can chronically activate A2B receptors to suppress Rap1B prenylation and signaling at the cell membrane, resulting in reduced cell-cell contact and promoting cell scattering. Inhibiting A2B receptors may be an effective method to prevent metastasis.
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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.