The MAP kinase-interacting kinases (MNKs) as targets in oncology

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Introduction: The mitogen-activated protein kinase (MAPK)-interacting kinases (MNKs) are switched on by the oncogenic MAPK (ERK) signalling pathway. They phosphorylate eukaryotic initiation factor (eIF) 4E, a protein which recruits ribosomes to mRNAs and thereby mediates their translation. Importantly, overexpression of eIF4E can transform cells, and its function is controlled by a second oncogenic pathway, mechanistic target of rapamycin complex 1. Areas covered: We have evaluated the literature related to the role of the MNKs in human cancers, including their control by oncogenic signalling pathways; their expression and regulation in cancer cells and preclinical cancer models; and their roles in the proliferation, survival and migration/invasion of cancer cells. We also discuss progress towards generating specific and potent inhibitors of the MNKs and data obtained using such compounds. Expert opinion: The available data indicate that MNKs and/or eIF4E phosphorylation play a role in oncogenic transformation, the progression of at least some tumours and especially in processes related to tumour metastasis. MNKs are clearly druggable targets and, as they are not essential, significant ‘side effects’ of inhibiting the MNKs are likely to be limited. Further work is required to assess the efficacy of MNK inhibition in tackling tumour development, progression and metastasis.

LanguageEnglish
Pages187-199
Number of pages13
JournalExpert Opinion on Therapeutic Targets
Volume23
Issue number3
DOIs
Publication statusPublished - 4 Mar 2019

Keywords

  • Cancer
  • MNKs
  • eIF4E
  • mRNA translation
  • metastasis
  • oncology
  • transformation

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

Cite this

@article{8dab522b1d53470993d16d7c40d44d1a,
title = "The MAP kinase-interacting kinases (MNKs) as targets in oncology",
abstract = "Introduction: The mitogen-activated protein kinase (MAPK)-interacting kinases (MNKs) are switched on by the oncogenic MAPK (ERK) signalling pathway. They phosphorylate eukaryotic initiation factor (eIF) 4E, a protein which recruits ribosomes to mRNAs and thereby mediates their translation. Importantly, overexpression of eIF4E can transform cells, and its function is controlled by a second oncogenic pathway, mechanistic target of rapamycin complex 1. Areas covered: We have evaluated the literature related to the role of the MNKs in human cancers, including their control by oncogenic signalling pathways; their expression and regulation in cancer cells and preclinical cancer models; and their roles in the proliferation, survival and migration/invasion of cancer cells. We also discuss progress towards generating specific and potent inhibitors of the MNKs and data obtained using such compounds. Expert opinion: The available data indicate that MNKs and/or eIF4E phosphorylation play a role in oncogenic transformation, the progression of at least some tumours and especially in processes related to tumour metastasis. MNKs are clearly druggable targets and, as they are not essential, significant ‘side effects’ of inhibiting the MNKs are likely to be limited. Further work is required to assess the efficacy of MNK inhibition in tackling tumour development, progression and metastasis.",
keywords = "Cancer, MNKs, eIF4E, mRNA translation, metastasis, oncology, transformation",
author = "Jianling Xie and Merrett, {James E.} and Jensen, {Kirk B.} and Proud, {Christopher G.}",
year = "2019",
month = "3",
day = "4",
doi = "10.1080/14728222.2019.1571043",
language = "English",
volume = "23",
pages = "187--199",
journal = "Expert Opinion on Therapeutic Targets",
issn = "1472-8222",
publisher = "Taylor and Francis Ltd.",
number = "3",

}

The MAP kinase-interacting kinases (MNKs) as targets in oncology. / Xie, Jianling; Merrett, James E.; Jensen, Kirk B.; Proud, Christopher G.

In: Expert Opinion on Therapeutic Targets, Vol. 23, No. 3, 04.03.2019, p. 187-199.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The MAP kinase-interacting kinases (MNKs) as targets in oncology

AU - Xie, Jianling

AU - Merrett, James E.

AU - Jensen, Kirk B.

AU - Proud, Christopher G.

PY - 2019/3/4

Y1 - 2019/3/4

N2 - Introduction: The mitogen-activated protein kinase (MAPK)-interacting kinases (MNKs) are switched on by the oncogenic MAPK (ERK) signalling pathway. They phosphorylate eukaryotic initiation factor (eIF) 4E, a protein which recruits ribosomes to mRNAs and thereby mediates their translation. Importantly, overexpression of eIF4E can transform cells, and its function is controlled by a second oncogenic pathway, mechanistic target of rapamycin complex 1. Areas covered: We have evaluated the literature related to the role of the MNKs in human cancers, including their control by oncogenic signalling pathways; their expression and regulation in cancer cells and preclinical cancer models; and their roles in the proliferation, survival and migration/invasion of cancer cells. We also discuss progress towards generating specific and potent inhibitors of the MNKs and data obtained using such compounds. Expert opinion: The available data indicate that MNKs and/or eIF4E phosphorylation play a role in oncogenic transformation, the progression of at least some tumours and especially in processes related to tumour metastasis. MNKs are clearly druggable targets and, as they are not essential, significant ‘side effects’ of inhibiting the MNKs are likely to be limited. Further work is required to assess the efficacy of MNK inhibition in tackling tumour development, progression and metastasis.

AB - Introduction: The mitogen-activated protein kinase (MAPK)-interacting kinases (MNKs) are switched on by the oncogenic MAPK (ERK) signalling pathway. They phosphorylate eukaryotic initiation factor (eIF) 4E, a protein which recruits ribosomes to mRNAs and thereby mediates their translation. Importantly, overexpression of eIF4E can transform cells, and its function is controlled by a second oncogenic pathway, mechanistic target of rapamycin complex 1. Areas covered: We have evaluated the literature related to the role of the MNKs in human cancers, including their control by oncogenic signalling pathways; their expression and regulation in cancer cells and preclinical cancer models; and their roles in the proliferation, survival and migration/invasion of cancer cells. We also discuss progress towards generating specific and potent inhibitors of the MNKs and data obtained using such compounds. Expert opinion: The available data indicate that MNKs and/or eIF4E phosphorylation play a role in oncogenic transformation, the progression of at least some tumours and especially in processes related to tumour metastasis. MNKs are clearly druggable targets and, as they are not essential, significant ‘side effects’ of inhibiting the MNKs are likely to be limited. Further work is required to assess the efficacy of MNK inhibition in tackling tumour development, progression and metastasis.

KW - Cancer

KW - MNKs

KW - eIF4E

KW - mRNA translation

KW - metastasis

KW - oncology

KW - transformation

UR - http://www.scopus.com/inward/record.url?scp=85060576855&partnerID=8YFLogxK

U2 - 10.1080/14728222.2019.1571043

DO - 10.1080/14728222.2019.1571043

M3 - Article

VL - 23

SP - 187

EP - 199

JO - Expert Opinion on Therapeutic Targets

T2 - Expert Opinion on Therapeutic Targets

JF - Expert Opinion on Therapeutic Targets

SN - 1472-8222

IS - 3

ER -