Molecular oncology. Causes of cancer and targets for treatment. Eds Edward P. Gelmann et al., Cambridge University Press (2014)
Hepatocyte growth factor (HGF), also known as scatter factor (SF), was discovered on the basis of its ability to promote liver regeneration, and independently for its mitogenic activity on epithelial cells and its ability to induce cell scatter (1). HGF is secreted primarily by mesenchymal cells and drives cell motility, proliferation, survival, and morphogenesis by binding to the Met receptor tyrosine kinase (TK) present on a variety of target cell types (1–6). HGF/Met signaling is critical for normal development and adult homeostasis: deletion of either gene lethally disrupts embryogenesis (4,6) and up-regulation of HGF expression after kidney, liver, or heart injury protects against tissue damage and promotes repair and regeneration in adults (1,7–11). Under normal conditions, Met activation is tightly regulated by paracrine ligand delivery, ligand activation, and receptor internalization, dephosphorylation, and degradation (1). Despite this, HGF/Met signaling contributes to tumorigenesis, tumor angiogenesis, and metastasis in several prevalent cancers, a realization that has driven rapid growth in the development of experimental therapeutics targeting the pathway.