Control of invasive growth by hepatocyte growth factor (HGF) and related scatter factors

Hepatocyte growth factor (HGF) is the prototype of a family of structurally related soluble molecules, named scatter factors (SFs). These control a complex genetic programme leading to cell-dissociation, migration in the extracellular matrix, growth, acquisition of polarity and tubule formation. This programme is pivotal during the embryonic development of epithelial and some mesodermal-derived tissues. In the adult HGF sustains cell survival and regeneration. A structurally related molecule, originally identified as macrophage stimulating protein (MSP), triggers the same complex genetic programme in epithelial and neural cells. The receptors for HGF and MSP are the tyrosine kinases encoded by the homologous genes MET and RON. As a distinctive feature, these receptors act via a two-phosphotyrosine docking site, capable of concomitant activation of multiple intracellular transducers and signalling pathways. In a number of malignant tumours, MET and RON constitutively sustain the genetic programme of scattering, leading to invasive growth and metastatic phenotype. Four MET-related receptors have been recently identified (the SEX protein family). These molecules are predominantly expressed during development and are likely to mediate repelling cues between cells of different type.