title: G Protein Coupled Receptor Kinase 3 Regulates Breast Cancer Migration, Invasion, and Metastasis.
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.
authors.affiliation: Thurston Arthritis Research Center and the Department of Medicine, Division of Rheumatology, Allergy, and Immunology, University of North Carolina, Chapel Hill, NC 27599, United States of America.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Billard
authors.affiliation: Thurston Arthritis Research Center and the Department of Medicine, Division of Rheumatology, Allergy, and Immunology, University of North Carolina, Chapel Hill, NC 27599, United States of America.
authors.forename: David J
authors.initials: DJ
authors.lastname: Fitzhugh
authors.affiliation: Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, United States of America.|Lineberger Comprehensive Cancer Center, University of North Carolina Chapel Hill, NC 27599, United States of America.
authors.forename: Joel S
authors.initials: JS
authors.lastname: Parker
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, 27599, United States of America.
authors.forename: Jaime M
authors.initials: JM
authors.lastname: Brozowski
authors.affiliation: Thurston Arthritis Research Center and the Department of Medicine, Division of Rheumatology, Allergy, and Immunology, University of North Carolina, Chapel Hill, NC 27599, United States of America.
authors.forename: Marcus W
authors.initials: MW
authors.lastname: McGinnis
authors.affiliation: Thurston Arthritis Research Center and the Department of Medicine, Division of Rheumatology, Allergy, and Immunology, University of North Carolina, Chapel Hill, NC 27599, United States of America.
authors.forename: Roman G
authors.initials: RG
authors.lastname: Timoshchenko
authors.affiliation: Thurston Arthritis Research Center and the Department of Medicine, Division of Rheumatology, Allergy, and Immunology, University of North Carolina, Chapel Hill, NC 27599, United States of America.
authors.forename: D Stephen
authors.initials: DS
authors.lastname: Serafin
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina Chapel Hill, NC 27599, United States of America.|Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599, United States of America.
authors.forename: Ruth
authors.initials: R
authors.lastname: Lininger
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina Chapel Hill, NC 27599, United States of America.|Department of Surgery, Division of Surgical Oncology, University of North Carolina, Chapel Hill, NC 27599, United States of America.
authors.forename: Nancy
authors.initials: N
authors.lastname: Klauber-Demore
authors.affiliation: Department of Developmental, Molecular & Chemical Biology, Tufts University, Medford, MA 02155, United States of America.
authors.forename: Gary
authors.initials: G
authors.lastname: Sahagian
authors.affiliation: Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599, United States of America.
authors.forename: Young K
authors.initials: YK
authors.lastname: Truong
authors.affiliation: Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599, United States of America.
authors.forename: Maria F
authors.initials: MF
authors.lastname: Sassano
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina Chapel Hill, NC 27599, United States of America.|Department of Medicine, Division of Hematology Oncology, University of North Carolina, Chapel Hill NC, 27599, United States of America.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Serody
authors.affiliation: Thurston Arthritis Research Center and the Department of Medicine, Division of Rheumatology, Allergy, and Immunology, University of North Carolina, Chapel Hill, NC 27599, United States of America.|Lineberger Comprehensive Cancer Center, University of North Carolina Chapel Hill, NC 27599, United States of America.|Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, 27599, United States of America.
authors.forename: Teresa K
authors.initials: TK
authors.lastname: Tarrant
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D005260:Female; D054770:G-Protein-Coupled Receptor Kinase 3 / Q000235:genetics / Q000502:physiology*; D020868:Gene Silencing; D006801:Humans; D051379:Mice; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis
chemical_list: D054770:G-Protein-Coupled Receptor Kinase 3