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Phosphorylation of eIF4E promotes EMT and metastasis via translational control of SNAIL and MMP-3

The progression of cancers from primary tumors to invasive and metastatic stages accounts for the overwhelming majority of cancer deaths. Understanding the molecular events which promote metastasis is thus critical in the clinic. Translational control is emerging as an important factor in tumorigene...

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Autores principales: Robichaud, Nathaniel, del Rincon, Sonia V., Huor, Bonnie, Alain, Tommy, Petruccelli, Andy, Hearnden, Jaclyn, Goncalves, Christophe, Grotegut, Stefan, Spruck, Charles H., Furic, Luc, Larsson, Ola, Miller, Wilson H., Sonenberg, Nahum
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4978545/
https://www.ncbi.nlm.nih.gov/pubmed/24909168
http://dx.doi.org/10.1038/onc.2014.146
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author Robichaud, Nathaniel
del Rincon, Sonia V.
Huor, Bonnie
Alain, Tommy
Petruccelli, Andy
Hearnden, Jaclyn
Goncalves, Christophe
Grotegut, Stefan
Spruck, Charles H.
Furic, Luc
Larsson, Ola
Miller, Wilson H.
Sonenberg, Nahum
author_facet Robichaud, Nathaniel
del Rincon, Sonia V.
Huor, Bonnie
Alain, Tommy
Petruccelli, Andy
Hearnden, Jaclyn
Goncalves, Christophe
Grotegut, Stefan
Spruck, Charles H.
Furic, Luc
Larsson, Ola
Miller, Wilson H.
Sonenberg, Nahum
author_sort Robichaud, Nathaniel
collection PubMed
description The progression of cancers from primary tumors to invasive and metastatic stages accounts for the overwhelming majority of cancer deaths. Understanding the molecular events which promote metastasis is thus critical in the clinic. Translational control is emerging as an important factor in tumorigenesis. The mRNA cap-binding protein eIF4E is an oncoprotein that plays an important role in cancer initiation and progression. eIF4E must be phosphorylated to promote tumor development. However, the role of eIF4E phosphorylation in metastasis is not known. Here, we show that mice in which eIF4E cannot be phosphorylated are resistant to lung metastases in a mammary tumor model, and that cells isolated from these mice exhibit impaired invasion. We also demonstrate that TGFβ induces eIF4E phosphorylation to promote translation of Snail and Mmp-3 mRNAs, and the induction of epithelial-to-mesenchymal transition (EMT). Furthermore, we describe a new model wherein EMT induced by TGFβ requires translational activation via the non-canonical TGFβ signaling branch acting through eIF4E phosphorylation.
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spelling pubmed-49785452016-08-09 Phosphorylation of eIF4E promotes EMT and metastasis via translational control of SNAIL and MMP-3 Robichaud, Nathaniel del Rincon, Sonia V. Huor, Bonnie Alain, Tommy Petruccelli, Andy Hearnden, Jaclyn Goncalves, Christophe Grotegut, Stefan Spruck, Charles H. Furic, Luc Larsson, Ola Miller, Wilson H. Sonenberg, Nahum Oncogene Article The progression of cancers from primary tumors to invasive and metastatic stages accounts for the overwhelming majority of cancer deaths. Understanding the molecular events which promote metastasis is thus critical in the clinic. Translational control is emerging as an important factor in tumorigenesis. The mRNA cap-binding protein eIF4E is an oncoprotein that plays an important role in cancer initiation and progression. eIF4E must be phosphorylated to promote tumor development. However, the role of eIF4E phosphorylation in metastasis is not known. Here, we show that mice in which eIF4E cannot be phosphorylated are resistant to lung metastases in a mammary tumor model, and that cells isolated from these mice exhibit impaired invasion. We also demonstrate that TGFβ induces eIF4E phosphorylation to promote translation of Snail and Mmp-3 mRNAs, and the induction of epithelial-to-mesenchymal transition (EMT). Furthermore, we describe a new model wherein EMT induced by TGFβ requires translational activation via the non-canonical TGFβ signaling branch acting through eIF4E phosphorylation. 2014-06-09 2015-04-16 /pmc/articles/PMC4978545/ /pubmed/24909168 http://dx.doi.org/10.1038/onc.2014.146 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Robichaud, Nathaniel
del Rincon, Sonia V.
Huor, Bonnie
Alain, Tommy
Petruccelli, Andy
Hearnden, Jaclyn
Goncalves, Christophe
Grotegut, Stefan
Spruck, Charles H.
Furic, Luc
Larsson, Ola
Miller, Wilson H.
Sonenberg, Nahum
Phosphorylation of eIF4E promotes EMT and metastasis via translational control of SNAIL and MMP-3
title Phosphorylation of eIF4E promotes EMT and metastasis via translational control of SNAIL and MMP-3
title_full Phosphorylation of eIF4E promotes EMT and metastasis via translational control of SNAIL and MMP-3
title_fullStr Phosphorylation of eIF4E promotes EMT and metastasis via translational control of SNAIL and MMP-3
title_full_unstemmed Phosphorylation of eIF4E promotes EMT and metastasis via translational control of SNAIL and MMP-3
title_short Phosphorylation of eIF4E promotes EMT and metastasis via translational control of SNAIL and MMP-3
title_sort phosphorylation of eif4e promotes emt and metastasis via translational control of snail and mmp-3
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4978545/
https://www.ncbi.nlm.nih.gov/pubmed/24909168
http://dx.doi.org/10.1038/onc.2014.146
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