Abstract
Mitogen-activated protein kinases (MAPKs) regulate diverse cellular processes including proliferation, cell survival, differentiation, and apoptosis. While conventional MAPK constituents have well-defined roles in oncogenesis, the MEK5 pathway has only recently emerged in cancer research. In this review, we consider the MEK5 signaling cascade, focusing specifically on its involvement in drug resistance and regulation of aggressive cancer phenotypes. Moreover, we explore the role of MEK5/ERK5 in tumorigenesis and metastatic progression, discussing the discrepancies in preclinical studies and assessing its viability as a therapeutic target for anti-cancer agents.
Keywords:
Cellular signaling; Kinase inhibitors; MEK5-ERK5; Mitogen-activated protein kinase; Targeted therapies.
Copyright © 2017 Elsevier B.V. All rights reserved.
Publication types
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Review
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Antineoplastic Agents / therapeutic use
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Apoptosis
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Cell Differentiation
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Cell Proliferation
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Drug Resistance, Neoplasm
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Humans
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MAP Kinase Kinase 5 / antagonists & inhibitors
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MAP Kinase Kinase 5 / genetics
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MAP Kinase Kinase 5 / metabolism*
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Mitogen-Activated Protein Kinase 7 / metabolism*
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Molecular Targeted Therapy
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Mutation
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Neoplasms / drug therapy
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Neoplasms / genetics
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Neoplasms / metabolism*
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Neoplasms / pathology
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Protein Kinase Inhibitors / therapeutic use
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism*
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Signal Transduction* / drug effects
Substances
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Antineoplastic Agents
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Protein Kinase Inhibitors
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Proto-Oncogene Proteins
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MAPK7 protein, human
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Mitogen-Activated Protein Kinase 7
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MAP Kinase Kinase 5
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MAP2K5 protein, human