G Protein Coupled Receptor Kinase 3 Regulates Breast Cancer Migration, Invasion, and Metastasis
| Autor: | David J. Fitzhugh, M.W. McGinnis, Roman G. Timoshchenko, Joel S. Parker, Jaime M. Brozowski, D. Stephen Serafin, Nancy Klauber-DeMore, Jonathan S. Serody, G. Gary Sahagian, Young K. Truong, Ruth A. Lininger, Teresa K. Tarrant, Maria F. Sassano, Matthew J. Billard |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Oncology Chemokine G-Protein-Coupled Receptor Kinase 3 lcsh:Medicine CXCR4 Biochemistry Metastasis Chemokine receptor Mice 0302 clinical medicine Cell Signaling Breast Tumors Basic Cancer Research Medicine and Health Sciences Neoplasm Metastasis lcsh:Science Triple-negative breast cancer Multidisciplinary Chemotaxis Animal Models 3. Good health Cancer Cell Migration Cell Motility 030220 oncology & carcinogenesis Female Chemokines Research Article Signal Transduction medicine.medical_specialty Transmembrane Receptors Mouse Models Breast Neoplasms Cell Migration Biology Research and Analysis Methods 03 medical and health sciences Breast cancer Model Organisms Internal medicine Breast Cancer medicine Animals Humans Neoplasm Invasiveness Gene Silencing G protein-coupled receptor G protein-coupled receptor kinase lcsh:R Cancers and Neoplasms Biology and Life Sciences Proteins Cell Biology medicine.disease G-Protein Signaling 030104 developmental biology Cancer research biology.protein lcsh:Q G Protein Coupled Receptors Developmental Biology |
| Zdroj: | PLoS ONE, Vol 11, Iss 4, p e0152856 (2016) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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