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  • The c-MET oncoprotein: Function, mechanisms of degradation and its targeting by novel anti-cancer agents

    Author(s)
    Park, Kyung Chan
    Richardson, Des R
    Griffith University Author(s)
    Richardson, Des R.
    Year published
    2020
    Metadata
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    Abstract
    Background: The c-MET oncoprotein drives cancer progression in a variety of tumors through its signaling transduction pathways. This oncoprotein is also degraded by multiple mechanisms involving the lysosome, proteasome and cleavage by proteases. Targeting c-MET degradation pathways may result in effective therapeutic strategies. Scope of review: Since the discovery of oncogenic functions of c-MET, there has been a great deal of effort to develop anti-cancer drugs targeting this oncoprotein. Unexpectedly, novel di-2-pyridylketone thiosemicarbazones that demonstrate marked anti-tumor activity, down-regulate c-MET through their ...
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    Background: The c-MET oncoprotein drives cancer progression in a variety of tumors through its signaling transduction pathways. This oncoprotein is also degraded by multiple mechanisms involving the lysosome, proteasome and cleavage by proteases. Targeting c-MET degradation pathways may result in effective therapeutic strategies. Scope of review: Since the discovery of oncogenic functions of c-MET, there has been a great deal of effort to develop anti-cancer drugs targeting this oncoprotein. Unexpectedly, novel di-2-pyridylketone thiosemicarbazones that demonstrate marked anti-tumor activity, down-regulate c-MET through their ability to bind intracellular iron and via mechanisms including, down-regulation of MET mRNA, enhanced lysosomal processing and increased metalloprotease-mediated cleavage. Major conclusions: The c-MET oncoprotein regulation and degradation pathways are complex. However, with increasing understanding of its degradation mechanisms, there is also greater opportunities to therapeutically target these pathways. General significance: Understanding the mechanisms of degradation of c-MET protein and its regulation could lead to novel therapeutics.
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    Journal Title
    Biochimica et Biophysica Acta (BBA) - General Subjects
    Volume
    1864
    Issue
    10
    DOI
    https://doi.org/10.1016/j.bbagen.2020.129650
    Subject
    Biochemistry and Cell Biology
    Pharmacology and Pharmaceutical Sciences
    Science & Technology
    Life Sciences & Biomedicine
    Biophysics
    c-MET
    Molecular Biology
    Publication URI
    http://hdl.handle.net/10072/400935
    Collection
    • Journal articles

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