title: The role of the HGF/Met axis in mesothelioma.
abstract: Malignant mesothelioma is an asbestos-related cancer that occurs most commonly in the pleural space and is incurable. Increasing evidence suggests that aberrant receptor tyrosine kinase (RTK)-directed signalling plays a key role in the pathogenesis of this cancer. In the majority of mesotheliomas, up-regulated expression or signalling by Met, the receptor for hepatocyte growth factor (HGF) can be demonstrated. Following binding of ligand, Met relays signals that promote cell survival, proliferation, movement, invasiveness, branching morphogenesis and angiogenesis. Here we describe the HGF/Met axis and review the mechanisms that lead to the aberrant activation of this signalling system in mesothelioma. We also describe the cross-talk that occurs between HGF/Met and a number of other receptors, ligands and co-receptor systems. The prevalent occurrence of HGF/Met dysregulation in patients with mesothelioma sets the scene for the investigation of pharmaceutical inhibitors of this axis. In light of the inter-relationship between HGF/Met and other ligand receptor, combinatorial targeting strategies may provide opportunities for therapeutic advancement in this challenging tumour.
authors.affiliation: King's College London, King's Health Partners Integrated Cancer Centre, Department of Research Oncology, Guy's Hospital Campus, Great Maze Pond, London SE1 9RT, U.K. Thivyan.t.thayaparan@kcl.ac.uk.
authors.forename: Thivyan
authors.initials: T
authors.lastname: Thayaparan
authors.affiliation: King's College London, King's Health Partners Integrated Cancer Centre, Department of Research Oncology, Guy's Hospital Campus, Great Maze Pond, London SE1 9RT, U.K. Department of Medical Oncology, Guy's and St Thomas' Hospital, NHS Foundation Trust, Great Maze Pond, London SE1 9RT, U.K.
authors.forename: James F
authors.initials: JF
authors.lastname: Spicer
authors.affiliation: King's College London, King's Health Partners Integrated Cancer Centre, Department of Research Oncology, Guy's Hospital Campus, Great Maze Pond, London SE1 9RT, U.K. Department of Immunology, Royal Free NHS Foundation Trust, Barnet Hospital, Hertfordshire EN5 3DJ, U.K. Department of Clinical Immunology and Allergy, King's College Hospital NHS Foundation Trust, Denmark Hill, London SE5 9RS, U.K.
authors.forename: John
authors.initials: J
authors.lastname: Maher
mesh_terms: D000818:Animals; D017228:Hepatocyte Growth Factor / Q000502:physiology*; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000503:physiopathology*; D008654:Mesothelioma / Q000473:pathology / Q000503:physiopathology*; D000086002:Mesothelioma, Malignant; D009154:Mutation; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000502:physiology*
chemical_list: C066855:HGF protein, human; D017228:Hepatocyte Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
keywords: Met; hepatocyte growth factor; malignant mesothelioma; receptor tyrosine kinase; scatter factor