Met endosomal signalling: In the right place, at the right time

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...

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Bibliographic Details
Published in:The international journal of biochemistry & cell biology 2014-04, Vol.49, p.69-74
Main Authors: Barrow-McGee, Rachel, Kermorgant, Stéphanie
Format: Article
Language:English
Subjects:
Activation
c-Met
Cancer
Cell migration
Cell Transformation, Neoplastic - genetics
Cell Transformation, Neoplastic - metabolism
Endocytosis - genetics
Endocytosis - physiology
Endosome
Endosomes - metabolism
Humans
Kinases
Models, Biological
Mutation
Proto-Oncogene Proteins c-met - genetics
Proto-Oncogene Proteins c-met - metabolism
Recycling
Signal Transduction - genetics
Signal Transduction - physiology
Signalling
Therapy
Transformations
Tyrosine
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Summary: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.
ISSN:1357-2725
1878-5875
DOI:10.1016/j.biocel.2014.01.009