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

      Journal of Cellular Biochemistry
      Animals, Extracellular Matrix, metabolism, Hepatocyte Growth Factor, Humans, Morphogenesis, Neoplasm Invasiveness, Neoplasms, pathology, Protein-Tyrosine Kinases, Proto-Oncogene Proteins c-met, Signal Transduction, physiology

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          Abstract

          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. Copyright 2002 Wiley-Liss, Inc.

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