ArticleJournal of immunology (Baltimore, Md. : 1950)2013
G protein-coupled receptor kinase 6 deficiency promotes angiogenesis, tumor progression, and metastasis.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 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.
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Who cites it
27 citing papers in PubMed, 41 citations in OpenAlex.
- Cell-based and isoform-selective G protein-coupled receptor kinase assays for comprehensive inhibitor evaluation.Communications biology · 2026Article
- GRK6 palmitoylation dictates triple-negative breast cancer metastasis via recruiting the β-Arrestin 2/MAPKs/NF-κB signaling axis.Breast cancer research : BCR · 2024Article
- Transcriptome signatures of host tissue infected with African swine fever virus reveal differential expression of associated oncogenes.Archives of virology · 2024Review
- Macrophage and Neutrophil Interactions in the Pancreatic Tumor Microenvironment Drive the Pathogenesis of Pancreatic Cancer.Cancers · 2021Review
- Tertiary butylhydroquinone alleviated liver steatosis and increased cell survival via β-arrestin-2/PI3K/AKT pathway.Iranian journal of basic medical sciences · 2021Article
- The Emerging Role of Epigenetic Mechanisms in the Causation of Aberrant MMP Activity during Human Pathologies and the Use of Medicinal Drugs.Biomolecules · 2021Review
- The GRKs Reactome: Role in Cell Biology and Pathology.International journal of molecular sciences · 2021Review
- Article
- Differential Regulation of GPCRs-Are GRK Expression Levels the Key?Frontiers in cell and developmental biology · 2021Review
- Significant association between high serum CCL5 levels and better disease-free survival of patients with early breast cancer.Cancer science · 2020Article
- Article
- How do chemokines navigate neutrophils to the target site: Dissecting the structural mechanisms and signaling pathways.Cellular signalling · 2019Review
- The role of G protein-coupled receptor kinases in the pathology of malignant tumors.Acta pharmacologica Sinica · 2018Review
- Overexpression of GRK6 associates with the progression and prognosis of colorectal carcinoma.Oncology letters · 2018Article
- The Role of G Protein-coupled Receptor Kinases in Cancer.International journal of biological sciences · 2018Review
- Role of G protein-coupled receptor kinase-6 inPhysiological genomics · 2017Article
- G Protein-Coupled Receptor Kinases in the Inflammatory Response and Signaling.Advances in immunology · 2017Review
- Prognostic value of decreased GRK6 expression in lung adenocarcinoma.Journal of cancer research and clinical oncology · 2016Article
- MMP-2 gene polymorphisms are associated with type A aortic dissection and aortic diameters in patients.Medicine · 2016Observational
- Controlled release strategy of paclitaxel by conjugating to matrix metalloproteinases-2 sensitive peptide.Oncotarget · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
G protein-coupled receptor kinases (GRKs) phosphorylate the activated form of G protein-coupled receptors leading to receptor desensitization and downregulation. We have recently shown that the chemokine receptor, CXCR2, couples to GRK6 to regulate cellular responses including chemotaxis, angiogenesis, and wound healing. In this study, we investigate the role of GRK6 in tumorigenesis using murine models of human lung cancer. Mice deficient in GRK6 (GRK6(-/-)) exhibited a significant increase in Lewis lung cancer growth and metastasis relative to control littermates (GRK6(+/+)). GRK6 deletion had no effect on the expression of proangiogenic chemokine or vascular endothelial growth factor, but upregulated matrix metalloproteinase (MMP)-2 and MMP-9 release, tumor-infiltrating PMNs, and microvessel density. Because β-arrestin-2-deficient (βarr2(-/-)) mice exhibited increased Lewis lung cancer growth and metastasis similar to that of GRK6(-/-), we developed a double GRK6(-/-)/βarr2(-/-) mouse model. Surprisingly, GRK6(-/-)/βarr2(-/-) mice exhibited faster tumor growth relative to GRK6(-/-) or βarr2(-/-) mice. Treatment of the mice with anti-CXCR2 Ab inhibited tumor growth in both GRK6(-/-) and GRK6(-/-)/βarr2(-/-) animals. Altogether, the results indicate that CXCR2 couples to GRK6 to regulate angiogenesis, tumor progression, and metastasis. Deletion of GRK6 increases the activity of the host CXCR2, resulting in greater PMN infiltration and MMP release in the tumor microenvironment, thereby promoting angiogenesis and metastasis. Because GRK6(-/-)/βarr2(-/-) showed greater tumor growth relative to GRK6(-/-) or βarr2(-/-) mice, the data further suggest that CXCR2 couples to different mechanisms to mediate tumor progression and metastasis.
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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.