17 General introduction pair facilitates invasive growth, through activation of a complex network of signaling cascades (74). During invasive growth, cancer cells combine proliferation, survival, motility, and epithelial-to-mesenchymal transition (EMT) (Figure 3) (71, 74). The latter process transforms epithelial cells into more mesenchymal derivatives, which is essential for physiological and pathological processes (75). More specifically, processes such as tissue development and regeneration, as well as the dissemination of cancer cells (71-73). Figure 3: HGF - MET signaling, mediated through RAS, PI3K, and STAT, facilitates the invasive growth of cancer cells. The human MET gene has been mapped to chromosome 7, location 7q31.2 (76). Its length spans over 120 kb, consisting of 21 exons, of which 20 coding, and 20 introns (77). The receptor counts 1408 amino acids and is synthesized as a partially glycosylated 170 kDa single-chain intracellular precursor, which is subjective to cleavage and further glycosylation yielding a mature, cell surface-associated 190 kDa disulfide linked single-pass heterodimer that consists of an extracellular NH2-terminal 50 kDa α-chain and a transmembranous 145 kDa β-chain. It is the β-chain that contains intrinsic, ligand-activated tyrosine kinase activity in its intracellular domain (77-79). 1
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