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)
Year published
2020
Metadata
Show full item recordAbstract
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 ...
View more >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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View more >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
Subject
Biochemistry and Cell Biology
Pharmacology and Pharmaceutical Sciences
Science & Technology
Life Sciences & Biomedicine
Biophysics
c-MET
Molecular Biology