title: CXCR4 suppression attenuates EGFRvIII-mediated invasion and induces p38 MAPK-dependent protein trafficking and degradation of EGFRvIII in breast cancer cells.
abstract: Our previous report has shown that the constitutively activated EGFR variant, EGFRvIII, up-regulates the pro-metastatic chemokine receptor CXCR4 in breast cancer cells. Here we evaluated the biological effect and cell signaling effects of silencing CXCR4 expression in EGFRvIII-expressing breast cancer cells. Short hairpin RNA (shRNA)-mediated suppression of CXCR4 expression significantly reduced the invasive potential and proliferation of EGFRvIII-expressing breast cancer cells. These cells exhibited a reduction of EGFRvIII activity and protein expression due to increased protein degradation and altered protein trafficking. In conclusion, suppression of CXCR4 inhibits EGFRvIII-mediated breast cancer cell invasion and proliferation.
authors: Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University Medical Center, Washington, DC 20057, United States.
authors: Massod
authors: M
authors: Rahimi
authors: Theodore A
authors: TA
authors: Toth
authors: Careen K
authors: CK
authors: Tang
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002469:Cell Separation; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D021381:Protein Transport; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D019718:Receptors, CXCR4; C410723:epidermal growth factor receptor VIII; D066246:ErbB Receptors; D048051:p38 Mitogen-Activated Protein Kinases; D046988:Proteasome Endopeptidase Complex