HGF/SF‐met signaling in the control of branching morphogenesis and invasion

Hepatocyte growth factor/Scatter factor (HGF/SF) is a multifunctional growth factor which can induce diverse biological events. In vitro, these include scattering, invasion, proliferation and branching morphogenesis. In vivo, HGF/SF is responsible for many processes during embryonic development and a variety of activities in adults, and many of these normal activities have been implicated in its role in tumorgenesis and metastasis. The c‐Met receptor tyrosine kinase is the only known receptor for HGF/SF and mediates all HGF/SF induced biological activities. Upon HGF/SF stimulation, the c‐Met receptor is tyrosine‐phosphorylated which is followed by the recruitment of a group of signaling molecules and/or adaptor proteins to its cytoplasmic domain and its multiple docking sites. This action leads to the activation of several different signaling cascades that form a complete network of intra and extracellular responses. Different combinations of signaling pathways and signaling molecules and/or differences in magnitude of responses contribute to these diverse series of HGF/SF‐Met induced activities and most certainly are influenced by cell type as well as different cellular environments. In this review, we focus on HGF/SF‐induced branching morphogenesis and invasion, and bring together recent new findings which provide insight into how HGF/SF, via c‐Met induces this response. J. Cell. Biochem. 88: 408–417, 2003. © 2002 Wiley‐Liss, Inc.