Abstract #2215: CXCL11 and CXCL12 modulate ERK1/2 and NF-kB activation in breast cancer cells via CXCR3, CXCR4, and CXCR7

Most breast cancer related deaths are because of metastasis. In order to achieve the metastatic goal; cancer cells must disseminate from the primary tumor site, migrate, invade, adhere, and survive during the process as well as at secondary homing sites. Chemokines, such as stromal cell-derived factor-1 (SDF-1; CXCL12) and interferon-inducible T cell \#945;-chemoattractant (I-TAC; CXCL11), and their receptors CXCR4, CXCR7 (CXCL11 & CXCL12), and CXCR3, respectively, are believed to play crucial roles in metastatic process by G protein coupled signaling events leading to the activation of transcription factors. Our study investigates the CXCL12:CXCR4/CXCR7 axis as well as the CXCL11:CXCR3/CXCR7 axis effects on pathways known to mediate transcriptional activation of BrCa cell invasion mechanisms. Amnis ImageStream analysis revealed that treatment of MCF-7 and MDA-MB-231 cell lines with either CXCL11 or CXCL12 resulted in the activation and translocation of ERK1/2 and NF-kB to the nucleus. FACE assay analysis demonstrated that stimulation with these chemokines selectively induced ERK1/2 and NFkB phosphorylation through FAK-, Src-, and/or PI3K-dependent pathways. These findings suggest that CXCL11 and CXCL12 differentially induces signal transduction through CXCR3/CXCR4/CXCR7. [This study was supported by funds from the Smith & Lucille Gibson Endowment and National Institute of Health Grants CA092078, CA086359, and MD00525.]

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2215.