CXCR4 suppression attenuates EGFRvIII-mediated invasion and induces p38 MAPK-dependent protein trafficking and degradation of EGFRvIII in breast cancer cells.

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.