%0 Journal Article
%T Notch signals in the endothelium and cancer "stem-like" cells: opportunities for cancer therapy
%A Jian-Wei Gu
%A Paola Rizzo
%A Antonio Pannuti
%A Todd Golde
%A Barbara Osborne
%A Lucio Miele
%J Vascular Cell
%D 2012
%I BioMed Central
%R 10.1186/2045-824x-4-7
%X The endothelium is a key regulator of vascular integrity and function. Endothelial cell functions and gene expression profiles are controlled by cytokines, hormones and metabolic products, as well as by mechanical stimuli such as shear stress caused by changes in blood flow [1]. Endothelial cells play a major role in the creation of supplemental blood vessels in ischemic tissues following vascular obstruction. This process is "hijacked" by cancer, which depends on neo-angiogenesis and vasculogenesis for growth and invasion. Endothelial cells are also an important component of the "vascular niche" for cancer stem-like cells (CSC) [2]. A number of pathways, including vascular endothelial growth factor (VEGF) and its receptors (VEGFRs), basic fibroblast growth factor (bFGF), transforming growth factor beta (TGF¦Â), and platelet-derived growth factor (PDGF) with their receptors, angiopoietin/Tie and ephrin/Eph, regulate vasculogenesis and angiogenesis [3]. Notch signaling, directly or by cross-talking with other pathways, plays a major role in modulating endothelial cells functions [4]. Additionally, Notch signaling has emerged as one of the master pathways in CSC [5]. This review summarizes the current data on the effects of Notch signaling in endothelial cells and CSC and how this modulation can be exploited for therapeutic purposes.Notch signaling is a highly conserved pathway that controls cell fate decisions in metazoans from invertebrates to mammals [6,7]. It is a short range communication system between two adjacent cells, based on ligand-activated receptors. In mammals there are four paralog receptors (Notch1, -2, -3 and -4) and five canonical ligands (Delta-like or DLL1, 3, 4 and Jagged1 and 2). Both receptors and ligands are type I membrane-spanning proteins Receptors are heterodimers consisting of an extracellular subunit (NEC) non-covalently bound to a transmembrane subunit (N£¿). Both subunits derive from a single precursor that is cleaved in the trans-Golgi
%U http://www.vascularcell.com/content/4/1/7