title: c-Met expression and activity in urogenital cancers - novel aspects of signal transduction and medical implications.
abstract: C-Met is a receptor tyrosine kinase with multiple functions throughout embryonic development, organogenesis and wound healing and is expressed in various epithelia. The ligand of c-Met is Hepatocyte Growth Factor (HGF) which is secreted among others by mesenchymal stroma/stem (MSC) cells.Physiological c-Met functions are centred around processes that underly cellular motility and invasive growth. Aberrant c-Met expression and activity is observed in numerous cancers and makes major contributions to cell malignancy. Importantly, HGF/c-Met signaling is crucial in the context of communication between cancer cells and the the tumor stroma.Here, we review recent findings on roles of dysregulated c-Met in urogenital tumors such as cancers of the urinary bladder, prostate, and ovary. We put emphasis on novel aspects of cancer-associated c-Met expression regulation on both, HGF-dependent and HGF-independent non-canonical mechanisms. Moreover, this review focusses on c-Met-triggered signalling with potential relevance for urogenital oncogenesis, and on strategies to specifically inhibit c-Met activity.
authors.affiliation: Biochemistry and Tumor Biology Lab, Department of Gynecology, Hannover Medical School, Hannover, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Hass
authors.affiliation: Institute of Biochemistry II, University Hospital Jena, Nonnenplan 2-4, D-07743, Jena, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Jennek
authors.affiliation: Biochemistry and Tumor Biology Lab, Department of Gynecology, Hannover Medical School, Hannover, Germany.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Institute of Biochemistry II, University Hospital Jena, Nonnenplan 2-4, D-07743, Jena, Germany. KarlHeinz.Friedrich@med.uni-jena.de.
authors.forename: Karlheinz
authors.initials: K
authors.lastname: Friedrich
mesh_terms: D000818:Animals; D006801:Humans; D008954:Models, Biological; D019859:Proto-Oncogene Proteins c-met / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction; D014565:Urogenital Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D019859:Proto-Oncogene Proteins c-met
keywords: Bladder, prostate and ovarian cancer; HGF/SF signalling; MSC; c-Met; c-Met inhibitors