The function, proteolytic processing, and histopathology of Met in cancer.
The hepatocyte growth factor (HGF) and its receptor, the Met receptor tyrosine kinase, form a signaling network promoting cell proliferation, invasion, and survival in normal and cancer cells. Improper regulation of this pathway is attributed to many cancer types through overexpression, activating mutations, or autocrine loop formation. Many studies describe the localization of Met as membranous/cytoplasmic, but some studies using antibodies targeted to the C-terminal domain of Met report nuclear localization. This chapter seeks to highlight the histopathology and expression of Met in cancer and its association with clinicopathological characteristics. We also discuss recent studies of the proteolytic processing of Met and effects of the processing on the subcellular localization of Met. Finally, we comment on Met as a therapeutic target for cancer treatment.
Hanna
Jason A
JA
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Bordeaux
Jennifer
J
Rimm
David L
DL
Agarwal
Seema
S
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000627:therapeutic use; D002467:Cell Nucleus / Q000378:metabolism; D016503:Drug Delivery Systems; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D011499:Protein Processing, Post-Translational; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology*; D019859:Proto-Oncogene Proteins c-met; D020239:Receptor Cross-Talk / Q000502:physiology; D017978:Receptors, Growth Factor / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology*
D000970:Antineoplastic Agents; D011518:Proto-Oncogene Proteins; D017978:Receptors, Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met