**2.1 Scattering and migration of tumor cells**

Initial events for the metastatic spread of tumors involve loss of cell-cell contact within the primary tumor mass. The integrity and morphology of epithelial tumor cell colonies are maintained by cell-cell contact mediated by cadherins and its associated intracellular catenin molecules. Cancer cells must lose their tight cell-to-cell contact by down-regulation of cadherin-cadherin complex during invasion into adjacent tissues. HGF induces scattering (*i.e*., dispersion of cluster cells into single cells) via an endocytosis of E-cadherin from cell surface to cytoplasma (Watabe *et al*., 1993; Miura *et al*., 2001). During cell migration, HGF activates the Ras-Rab5 pathway for endocytosis of cadherins (Kimura *et al*., 2006), which triggers nuclear localization of β-catenin, a transcription factor of genes responsible for cell motility (Hiscox & Jiang, 1999). Stimulation of an Rho small G protein cascade and activation of cdc42, rac and PAK by HGF leads to the disassembly of stress fiber or focal adhesions, while lamellipodia formation and cell spreading are enhanced by HGF (Royal *et al*., 2000). These changes confer a down-stream mechanism of MET-mediated cancer invasion.
