Role of c-MET in upper aerodigestive malignancies--from biology to novel therapies.
Overactivation and defective downregulation of receptor tyrosine kinase (RTK) pathways have been implicated in human carcinogenesis. RTKs represent an important class of anticancer novel therapeutic target. Some RTKs are known to be protooncogenes that can mediate signal transduction, alteration of reactive oxygen species (ROS), cellular proliferation, cell motility and migration, apoptosis, and survival. c-MET is a unique RTK that regulates a wide variety of cellular functions. c-MET has been shown to be overexpressed or mutated in a variety of human malignancies. Stimulation of c-MET via its natural ligand hepatocyte growth factor/ scatter factor (HGF/SF) leads to a plethora of biological and biochemical effects in the cell. Activation of c-MET signaling can lead to cell motility and scattering, angiogenesis, proliferation, branching morphogenesis, invasion, and eventual metastasis. This review summarizes the structure and functions of c-MET, with particular emphasis on its role in upper aerodigestive malignancies. The unique biological functions altered by c-MET and its mutations are discussed as well. Finally, c-MET, when mutated or overexpressed in malignant cells, serves as an important therapeutic target, and the most recent data with respect to its inhibition are also summarized in this review.
Dietrich
Sascha
S
Section of Hematology/Oncology, Department of Medicine, Pritzker School of Medicine, The University of Chicago, Chicago, Illinois 60637, USA.
Uppalapati
Radha
R
Seiwert
Tanguy Y
TY
Ma
Patrick C
PC
D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D018288:Carcinoma, Small Cell / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D004195:Disease Models, Animal; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D051379:Mice; D009154:Mutation; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D019859:Proto-Oncogene Proteins c-met