Abstract 2895: The epithelial to mesenchymal transition is associated with alterations in the mitogenic signaling pathways that drive cancer cell proliferation

Abstract The Epithelial to Mesenchymal Transition (EMT), by facilitating the metastatic process, is an important step in tumor progression for many types of cancer. We have developed a mouse tumor model, driven by the HER2/neu oncogene, whereby this process can be studied robustly both in vivo and in cell culture. This system has revealed significant changes in mitogenic signaling networks that occur during EMT. Post-EMT cancer cells acquired increased responsiveness to HGF, PDGF, and LPA. This change in responsiveness was accompanied by a decrease of Her2, c-Src and IRS-1 levels, as well as an increase in Axl, PDGFR and c-Met levels. Perturbations in these signaling cascades results in the differential sensitivity to certain anti-cancer therapeutics. Post-EMT cells were less sensitive than Pre-EMT cells to the MEK inhibitor U0126. Furthermore, while Pre-EMT cells exhibited cell cycle arrest in response to rapamycin, Post-EMT cell proliferation was stimulated. These observations may have significant bearing on the efficacy of targeted therapeutic agents in patients with metastatic breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2895. doi:10.1158/1538-7445.AM2011-2895