EGFR variant-mediated invasion by enhanced CXCR4 expression through transcriptional and post-translational mechanisms.

ABSTRACT: The expression of the potent, constitutively activated EGFR variant, EGFRvIII, has been linked to breast cancer metastasis, but the mechanisms of EGFRvIII and CXCR4 crosstalk, which may facilitate breast cancer invasion, have never been explored. Here we report that CXCR4 expression is increased in breast cancer cells expressing EGFRvIII regardless of the ER/PgR status of the cells. Treatment of EGFRvIII-expressing breast cancer cells with the tyrosine kinase inhibitor, AG1478, reverses CXCR4 expression back to levels expressed in parental cells. In addition, expressing EGFRvIII enhances CXCL12/CXCR4-mediated invasion, which can be inhibited by CXCR4 inhibitors. Surprisingly, CXCR4 mRNA and its transcriptional regulator, HIF-1alpha, are up-regulated only in ER+/PgR+ estrogen-dependent EGFR

SUBMITTER: Rahimi M 

PROVIDER: S-EPMC2917067 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature