Abstract 3322: Spatio-temporal regulation of epithelial transformation by mistrafficking of EGFR ligand, epiregulin

Abstract

Abstract The EGF receptor (EGFR) ligand epiregulin (EREG) is delivered preferentially to the basolateral cell surface of polarized MDCK cells. Recently, we showed that EREG basolateral trafficking is regulated by a conserved tyrosine residue within a YXXΦ motif (Y156ERV) in its cytoplasmic domain. Interestingly, a Y156A substitution led to apical mistrafficking of EREG and transformation of polarized MDCK cells (PNAS 110: 8960-5, 2013). We have identified EREG mutations (R147stop) in human tumors that would disrupt the basolateral sorting motif of EREG and now report that EREG harboring these patient mutations mistrafficks to the apical surface. We propose that ligand mistrafficking is a driver of transformation rather than being a mere passenger. To test our proposal wild-type and mutant EREG will be inducibly (Tet-ON) expressed at various stages of MDCK cyst formation and maintenance in 3D Matrigel cultures where we have now recapitulated the transformation phenotype induced by EREG-mistrafficking. Results from these experiments will be presented at the meeting. Citation Format: Bhuminder Singh, Galina Bogatcheva, Mary K. Washington, Robert J. Coffey. Spatio-temporal regulation of epithelial transformation by mistrafficking of EGFR ligand, epiregulin. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3322. doi:10.1158/1538-7445.AM2014-3322