G Protein Coupled Receptor Kinase 3 Regulates Breast Cancer Migration, Invasion, and Metastasis.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Billard, MJ; Fitzhugh, DJ; Parker, JS; Brozowski, JM; McGinnis, MW; Timoshchenko, RG; Serafin, DS; Lininger, R; Klauber-Demore, N; Sahagian, G; Truong, YK; Sassano, MF; Serody, JS; Tarrant, TK

Published Date

  • 2016

Published In

Volume / Issue

  • 11 / 4

Start / End Page

  • e0152856 -

PubMed ID

  • 27049755

Pubmed Central ID

  • PMC4822790

Electronic International Standard Serial Number (EISSN)

  • 1932-6203

Digital Object Identifier (DOI)

  • 10.1371/journal.pone.0152856


  • eng

Conference Location

  • United States