Format

Send to

Choose Destination
Int J Biochem Cell Biol. 2014 Apr;49:69-74. doi: 10.1016/j.biocel.2014.01.009. Epub 2014 Jan 16.

Met endosomal signalling: in the right place, at the right time.

Author information

1
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, United Kingdom.
2
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, United Kingdom. Electronic address: s.kermorgant@qmul.ac.uk.

Abstract

Deregulated signalling of the Receptor Tyrosine Kinase (RTK), Met, and/or its ligand HGF have been associated with cancer formation and progression to metastasis, with Met/HGF often overexpressed or mutated. Thus, Met has become a major target for cancer therapy and its inhibition is currently being tested in the clinic. It has recently become evident that, instead of signalling at the plasma membrane only, Met signals post-internalisation from endosomal compartments. Thus, Met endocytic trafficking is required for the full activation of signals such as Gab1, ERK 1/2, STAT3 and Rac1, all implicated in cell survival, invasion and metastasis. Modifications in the balance between degradation and recycling of Met may also impinge on Met signalling. Moreover, oncogenic Met mutations in the kinase domain trigger constitutive Met internalisation/recycling, leading to "endosomal signalling" and consequent cell transformation. Using Met as an example, this review outlines the evidence that the molecular mechanisms regulating trafficking and endosomal signalling may be exploited to design future cancer therapies.

KEYWORDS:

Cancer; Cell migration; Endosome; Signalling; c-Met

PMID:
24440758
DOI:
10.1016/j.biocel.2014.01.009
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center