G Protein Coupled Receptor Kinase 3 Regulates Breast Cancer Migration, Invasion, and Metastasis
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Billard, Matthew J, et al. G Protein Coupled Receptor Kinase 3 Regulates Breast Cancer Migration, Invasion, and Metastasis. 2016. https://doi.org/10.17615/gegf-p920APA
Billard, M., Fitzhugh, D., Parker, J., Brozowski, J., Mc Ginnis, M., Timoshchenko, R., Serafin, D., Lininger, R., Klauber Demore, N., Sahagian, G., Truong, Y., Sassano, M., Serody, J., & Tarrant, T. (2016). G Protein Coupled Receptor Kinase 3 Regulates Breast Cancer Migration, Invasion, and Metastasis. https://doi.org/10.17615/gegf-p920Chicago
Billard, Matthew J., David J Fitzhugh, Joel S Parker, Jaime M Brozowski, Marcus W Mc Ginnis, Roman G Timoshchenko, D. Stephen Serafin et al. 2016. G Protein Coupled Receptor Kinase 3 Regulates Breast Cancer Migration, Invasion, and Metastasis. https://doi.org/10.17615/gegf-p920- Creator
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Billard, Matthew J.
- Affiliation: School of Medicine, Department of Medicine
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Fitzhugh, David J.
- Affiliation: School of Medicine, Department of Medicine
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Parker, Joel S.
- Affiliation: School of Medicine, Department of Genetics
- Other Affiliation: University of North Carolina at Chapel Hill
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Brozowski, Jaime M.
- Affiliation: School of Medicine, Department of Microbiology and Immunology
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McGinnis, Marcus W.
- Affiliation: School of Medicine, Department of Medicine
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Timoshchenko, Roman G.
- Affiliation: School of Medicine, Department of Medicine
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Serafin, D. Stephen
- Affiliation: School of Medicine, Department of Medicine
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Lininger, Ruth
- Affiliation: University of North Carolina at Chapel Hill
- Other Affiliation: Department of Pathology and Laboratory Medicine
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Klauber-Demore, Nancy
- Affiliation: University of North Carolina at Chapel Hill
- Other Affiliation: Department of Surgery
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Sahagian, Gary
- Other Affiliation: Department of Developmental; Molecular and Chemical Biology; Tufts University
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Truong, Young K.
- Affiliation: Gillings School of Global Public Health, Department of Biostatistics
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Sassano, Maria F.
- Affiliation: School of Medicine, Department of Pharmacology
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Serody, Jonathan S.
- Affiliation: University of North Carolina at Chapel Hill
- Other Affiliation: Department of Medicine
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Tarrant, Teresa K.
- Affiliation: School of Medicine, Department of Medicine
- Other Affiliation: University of North Carolina at Chapel Hill
- Abstract
- Triple negative breast cancer (TNBC) is a heterogeneous disease that has a poor prognosis and limited treatment options. Chemokine receptor interactions are important modulators of breast cancer metastasis; however, it is now recognized that quantitative surface expression of one important chemokine receptor, CXCR4, may not directly correlate with metastasis and that its functional activity in breast cancer may better inform tumor pathogenicity. G protein coupled receptor kinase 3 (GRK3) is a negative regulator of CXCR4 activity, and we show that GRK expression correlates with tumorigenicity, molecular subtype, and metastatic potential in human tumor microarray analysis. Using established human breast cancer cell lines and an immunocompetent in vivo mouse model, we further demonstrate that alterations in GRK3 expression levels in tumor cells directly affect migration and invasion in vitro and the establishment of distant metastasis in vivo. The effects of GRK3 modulation appear to be specific to chemokine-mediated migration behaviors without influencing tumor cell proliferation or survival. These data demonstrate that GRK3 dysregulation may play an important part in TNBC metastasis.
- Date of publication
- 2016
- Keyword
- DOI
- Identifier
- Publisher DOI: https://doi.org/10.1371/journal.pone.0152856
- PMID: 27049755
- PMCID: PMC4822790
- Onescience id: 44f06220de9afe41fc142841f1539202cb39fa5c
- Resource type
- Article
- Rights statement
- In Copyright
- Journal title
- PloS One
- Journal volume
- 11
- Journal issue
- 4
- Page start
- e0152856
- Language
- English
- ISSN
- 1932-6203
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