MET: A critical player in tumorigenesis and therapeutic target

Abstract

Since its discovery more than 25 years ago, numerous studies have established that the MET receptor is unique among tyrosine kinases. Signaling through MET is necessary for normal development and for the progression of a wide range of human cancers. METactivation has been shownto drive numerous signaling pathways; however, it is not clear howMETsignaling mediates diverse cellular responses such as motility, invasion, growth, and angiogenesis. Great strides have been made in understanding the pleotropic aspects of MET signaling using three-dimensional molecular structures, cell culture systems, human tumors, and animal models. These combined approaches have driven the development of MET-targeted therapeutics that have shown promising results in the clinic. Here we examine the unique features of METand hepatocyte growth factor/scatter factor (HGF/SF) structure and signaling, mutational activation, genetic mouse models of MET and HGF/SF, and MET-targeted therapeutics. © 2013 Cold Spring Harbor Laboratory Press; all rights reserved.