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.
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April 2016
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Endoplasmic reticulumendosome contact sites. This pseudo-colored electron microscopy image shows the formation of inter-organelle membrane contact sites between late endosomes (magenta) and the endoplasmic reticulum (ER; green). This tethering results from the interaction between two ER-anchored proteins (VAP-A and VAP-B) and the late endosomeanchored protein STARD3NL. Mitochondria: brown; nucleus: blue. For further details see pp. 493-498. Image kindly provided by Fabien Alpy. - PDF Icon PDF LinkTable of Contents
Review Article|
April 11 2016
The role of the HGF/Met axis in mesothelioma
Thivyan Thayaparan;
Thivyan Thayaparan
1
*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.
1To whom correspondence should be addressed (email Thivyan.t.thayaparan@kcl.ac.uk).
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James F. Spicer;
James F. Spicer
*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.
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John Maher
John Maher
*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.
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Publisher: Portland Press Ltd
Received:
January 07 2016
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2016 Authors; published by Portland Press Limited
2016
Biochem Soc Trans (2016) 44 (2): 363–370.
Article history
Received:
January 07 2016
Citation
Thivyan Thayaparan, James F. Spicer, John Maher; The role of the HGF/Met axis in mesothelioma. Biochem Soc Trans 15 April 2016; 44 (2): 363–370. doi: https://doi.org/10.1042/BST20150252
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