The eIF4E2-Directed Hypoxic Cap-Dependent Translation Machinery Reveals Novel Therapeutic Potential for Cancer Treatment

Hypoxia is an aspect of the tumor microenvironment that is linked to radiation and chemotherapy resistance, metastasis, and poor prognosis. The ability of hypoxic tumor cells to achieve these cancer hallmarks is, in part, due to changes in their gene expression profiles. Cancer cells have a high dem...

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Autores principales: Melanson, Gaelan, Timpano, Sara, Uniacke, James
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5727761/
https://www.ncbi.nlm.nih.gov/pubmed/29317983
http://dx.doi.org/10.1155/2017/6098107
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author Melanson, Gaelan
Timpano, Sara
Uniacke, James
author_facet Melanson, Gaelan
Timpano, Sara
Uniacke, James
author_sort Melanson, Gaelan
collection PubMed
description Hypoxia is an aspect of the tumor microenvironment that is linked to radiation and chemotherapy resistance, metastasis, and poor prognosis. The ability of hypoxic tumor cells to achieve these cancer hallmarks is, in part, due to changes in their gene expression profiles. Cancer cells have a high demand for protein synthesis, and translational control is subsequently deregulated. Various mechanisms of translation initiation are active to improve the translation efficiency of select transcripts to drive cancer progression. This review will focus on a noncanonical cap-dependent translation initiation mechanism that utilizes the eIF4E homolog eIF4E2, a hypoxia-activated cap-binding protein that is implicated in hypoxic cancer cell migration, invasion, and tumor growth in mouse xenografts. A historical perspective about eIF4E2 and its various aliases will be provided followed by an evaluation of potential therapeutic strategies. The recent successes of disabling canonical translation and eIF4E with drugs should highlight the novel therapeutic potential of targeting the homologous eIF4E2 in the treatment of hypoxic solid tumors.
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spelling pubmed-57277612018-01-09 The eIF4E2-Directed Hypoxic Cap-Dependent Translation Machinery Reveals Novel Therapeutic Potential for Cancer Treatment Melanson, Gaelan Timpano, Sara Uniacke, James Oxid Med Cell Longev Review Article Hypoxia is an aspect of the tumor microenvironment that is linked to radiation and chemotherapy resistance, metastasis, and poor prognosis. The ability of hypoxic tumor cells to achieve these cancer hallmarks is, in part, due to changes in their gene expression profiles. Cancer cells have a high demand for protein synthesis, and translational control is subsequently deregulated. Various mechanisms of translation initiation are active to improve the translation efficiency of select transcripts to drive cancer progression. This review will focus on a noncanonical cap-dependent translation initiation mechanism that utilizes the eIF4E homolog eIF4E2, a hypoxia-activated cap-binding protein that is implicated in hypoxic cancer cell migration, invasion, and tumor growth in mouse xenografts. A historical perspective about eIF4E2 and its various aliases will be provided followed by an evaluation of potential therapeutic strategies. The recent successes of disabling canonical translation and eIF4E with drugs should highlight the novel therapeutic potential of targeting the homologous eIF4E2 in the treatment of hypoxic solid tumors. Hindawi 2017 2017-11-26 /pmc/articles/PMC5727761/ /pubmed/29317983 http://dx.doi.org/10.1155/2017/6098107 Text en Copyright © 2017 Gaelan Melanson et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Melanson, Gaelan
Timpano, Sara
Uniacke, James
The eIF4E2-Directed Hypoxic Cap-Dependent Translation Machinery Reveals Novel Therapeutic Potential for Cancer Treatment
title The eIF4E2-Directed Hypoxic Cap-Dependent Translation Machinery Reveals Novel Therapeutic Potential for Cancer Treatment
title_full The eIF4E2-Directed Hypoxic Cap-Dependent Translation Machinery Reveals Novel Therapeutic Potential for Cancer Treatment
title_fullStr The eIF4E2-Directed Hypoxic Cap-Dependent Translation Machinery Reveals Novel Therapeutic Potential for Cancer Treatment
title_full_unstemmed The eIF4E2-Directed Hypoxic Cap-Dependent Translation Machinery Reveals Novel Therapeutic Potential for Cancer Treatment
title_short The eIF4E2-Directed Hypoxic Cap-Dependent Translation Machinery Reveals Novel Therapeutic Potential for Cancer Treatment
title_sort eif4e2-directed hypoxic cap-dependent translation machinery reveals novel therapeutic potential for cancer treatment
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5727761/
https://www.ncbi.nlm.nih.gov/pubmed/29317983
http://dx.doi.org/10.1155/2017/6098107
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