Abstract 5406: The CendR pathway: A novel cell penetration and transcytosis pathway regulated by nutrient availability

Abstract

Abstract Transport of molecules across the vascular wall, through tissue, and into target cells plays an important role in various physiological and pathological processes. We previously described a novel class of tumor-targeting peptides (CendR peptides) that penetrate into cells and tumor tissue through an as yet incompletely characterized transport pathway initiated by peptide binding to neuropilin-1 (NRP1). This pathway has shown promise in enhancing drug delivery into tumors. Here we perform a genome-wide RNAi screen to identify components responsible for cell penetration of CendR peptides. We show that the binding of CendR peptides to NRP1 initiates a novel endocytic process that depends on a subset of genes and a transport route distinct from those of known endocytic pathways. Strikingly, we found the internalization of CendR peptides to be controlled by nutrient-sensing and cell growth-regulatory pathways. Nutrient deprivation stimulated the cell penetration and intercellular transport of CendR peptides, both in vitro and in vivo. These data suggest a physiological role for CendR pathway in nutrient sensing and transport. The ability to activate this pathway with peptides provides immediate applications to drug delivery. Citation Format: Hong-Bo Pang, Gary B. Braun, Tomas Friman, Pedro Aza-Blanc, Manuel E. Ruidiaz, Kazuki N. Sugahara, Tambet Teesalu, Erkki Ruoslahti. The CendR pathway: A novel cell penetration and transcytosis pathway regulated by nutrient availability. [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 5406. doi:10.1158/1538-7445.AM2014-5406