Hepatocyte Growth Factor Signaling in Cancer Metastasis

Tracey      A. Martin; Malcolm      D. Mason; Wen      G. Jiang

Abstract

Since their discovery in the late 1980s, Hepatocyte growth factor (HGF) and its receptor, c-MET, have become the focus of intense scrutiny as regards their role in cancer and metastasis [1, 2]. HGF is now known to be a potent morphogen that can regulate tissue and organ regeneration and modulate cell morphology, it is a motogen that can stimulate cell motility and migration, and is a mitogen able to regulate cell growth and death and is a powerful angiogenic and lymphangiogenic factor [3-5]. The diverse range of functions that can be ascribed to HGF/c-MET is transmitted via a variety of cell signaling pathways. This review will focus on recent work demonstrating the importance of HGF/c-MET in regulating these signaling events, how they are related to cancer metastasis and where they may be targeted for patient intervention.

Keywords: Cancer, HGF, Metastasis, Signaling, c-MET, intracellular signalling, Grb2/SOS, Gab1, PI3 kinase, Stat3, Wnt signaling, Rho/Rac, Protein Kinase C, protein tyrosine phosphates, MAPK, mTOR, ERK, Mcl-1, RAS, MEK, LKB1, Cdc42, Mig6, Phospholipase C g-, cRaf, Catenin, Paxillin, FAK