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RTKs as Models for Trafficking Regulation: c-Met/HGF Receptor-c-Met Signalling in Cancer—Location Counts

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Vesicle Trafficking in Cancer

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Abstract

c-Met, the receptor tyrosine kinase of Hepatocyte Growth Factor (HGF), plays a major role in tumour progression and constitutes an attractive target for cancer therapy. Upon ligand binding at the plasma membrane, c-Met triggers various signalling pathways, which promote cell responses such as proliferation, migration and survival. Recent studies have shown that HGF binding to c-Met also triggers a rapid endocytosis of c-Met, leading to its intracellular trafficking and ultimately degradation. However, c-Met remains bound to HGF and activated on endosomes and in fact its endocytosis is required for optimal signalling. Moreover c-Met exploits both its endocytosis and its subsequent intracellular trafficking to alter its signalling capacity. Finally, recent studies on oncogenic mutants of c-Met, reported in human cancers, have shown that activated c-Met accumulation on endosomes can lead to cell transformation. Here, we review the present knowledge about c-Met endocytosis and trafficking, the interplay between c-Met trafficking and signalling and the consequences on tumorigenesis. We discuss the idea that c-Met localisation, in addition to its activation, plays a key role in its signalling and possibly in cancer progression.

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Authors and Affiliations

  1. Spatial Signalling Team, Centre for Tumour Biology, Barts Cancer Institute—A Cancer Research UK Centre of Excellence, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London, EC1M 6BQ, UK

    Carine Joffre, Rachel Barrow, Ludovic Ménard & Stéphanie Kermorgant

  2. Institut Curie, INSERM U-830, 26 rue d’Ulm, 75248, Paris Cedex 05, France

    Carine Joffre

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  1. Carine Joffre
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  2. Rachel Barrow
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  3. Ludovic Ménard
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  4. Stéphanie Kermorgant
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Correspondence to Stéphanie Kermorgant .

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  1. Department of Biological Regulation, Candiotty Bldg, Hertzel St 1, Rehovot, 76100, Israel

    Yosef Yarden

  2. , Department of Biological Regulation, Weizmann Institute of Science, Hertzl Street 1, Rehovot, 76100, Israel

    Gabi Tarcic

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Joffre, C., Barrow, R., Ménard, L., Kermorgant, S. (2013). RTKs as Models for Trafficking Regulation: c-Met/HGF Receptor-c-Met Signalling in Cancer—Location Counts. In: Yarden, Y., Tarcic, G. (eds) Vesicle Trafficking in Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6528-7_13

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