Paradoxical action of growth factors: antiproliferative and proapoptotic signaling by HGF/c-MET.

Hepatocyte growth factor (HGF)/mesenchymal-epithelial transition factor (c-MET) signaling is usually associated with the promotion of cellular growth and often with progression of tumors. Nevertheless, under certain conditions HGF can also act as an antiproliferative and proapoptotic factor and can sensitize various cancer cells, treated with anticancer drugs, to apoptosis. Not only HGF but also its various truncated forms as well as intracellular fragments of its membrane receptor, c-MET, may act as antiproliferative and proapoptotic factors toward various cells. This review focuses on different mechanisms responsible for such paradoxical action of the known typical growth factor. It also points toward the possibilities of usage of this information in anticancer therapy.