Abstract 5202: MUC1 oncogene is required for EGF/Src-driven carcinoma cell metastasis

Epidermal growth factor receptor (EGFR) and Src tyrosine kinase signaling promote epithelial to mesenchymal transition (EMT) and have been associated with increased metastatic capacity of tumor cells. We observed that EGFR/Src signaling leads to the activation of integrin αvβ5 on carcinoma cells, resulting in an increased invasive capacity without influencing primary tumor growth in vivo (Ricono, et al 2009). We explored potential downstream effectors of Src that may influence this metastatic cascade using an in silico screening approach. Leads were selected based on their ability to influence EGFR/Src/αvβ5-dependent invasion in vitro and metastasis in vivo in a chicken chorioallantoic membrane model. Here, we report the transmembrane glycoprotein mucin-1 (MUC1) as an essential mediator of the EGFR/Src/αvβ5 signaling axis leading to the metastasis of carcinoma cells in vivo. Disruption of MUC1 expression selectively abolished EGF/Src/αvβ5-dependent migration in vitro and metastasis in vivo without influencing primary tumor growth. Importantly, EGFR- and Src-dependent phosphorylation of the cytoplasmic tail of MUC1 (MUC1-CT) facilitated cleavage of MUC1-CT. Once cleaved, MUC1-CT was able to associate with β-catenin, enter the nucleus and modulate gene expression relevant to the metastatic properties of these cells. These findings support a critical role for MUC1 in the regulation of EGFR/Src/αvβ5-dependent metastasis of a wide range of carcinomas. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5202.