Key contribution of CPEB4mediated translational control to cancer progression

Elena Ortiz-Zapater, David Pineda, Neus Martínez-Bosch, Gonzalo Fernández-Miranda, Mar Iglesias, Francesc Alameda, Mireia Moreno, Carolina Eliscovich, Eduardo Eyras, Francisco X. Real, Raúl Méndez, Pilar Navarro

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

Malignant transformation, invasion and angiogenesis rely on the coordinated reprogramming of gene expression in the cells from which the tumor originated. Although deregulated gene expression has been extensively studied at genomic and epigenetic scales, the contribution of the regulation of mRNA-specific translation to this reprogramming is not well understood. Here we show that cytoplasmic polyadenylation element binding protein 4 (CPEB4), an RNA binding protein that mediates meiotic mRNA cytoplasmic polyadenylation and translation, is overexpressed in pancreatic ductal adenocarcinomas and glioblastomas, where it supports tumor growth, vascularization and invasion. We also show that, in pancreatic tumors, the pro-oncogenic functions of CPEB4 originate in the translational activation of mRNAs that are silenced in normal tissue, including the mRNA of tissue plasminogen activator, a key contributor to pancreatic ductal adenocarcinoma malignancy. Taken together, our results document a key role for post-transcriptional gene regulation in tumor development and describe a detailed mechanism for gene expression reprogramming underlying malignant tumor progression.

Original languageEnglish (US)
Pages (from-to)83-90
Number of pages8
JournalNature Medicine
Volume18
Issue number1
DOIs
StatePublished - Jan 2012

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Tumors
Gene expression
Polyadenylation
Messenger RNA
Neoplasms
Carrier Proteins
Gene Expression
Adenocarcinoma
RNA-Binding Proteins
Tissue Plasminogen Activator
Protein Biosynthesis
Glioblastoma
Epigenomics
Chemical activation
Tissue
Growth
Genes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Ortiz-Zapater, E., Pineda, D., Martínez-Bosch, N., Fernández-Miranda, G., Iglesias, M., Alameda, F., ... Navarro, P. (2012). Key contribution of CPEB4mediated translational control to cancer progression. Nature Medicine, 18(1), 83-90. https://doi.org/10.1038/nm.2540

Key contribution of CPEB4mediated translational control to cancer progression. / Ortiz-Zapater, Elena; Pineda, David; Martínez-Bosch, Neus; Fernández-Miranda, Gonzalo; Iglesias, Mar; Alameda, Francesc; Moreno, Mireia; Eliscovich, Carolina; Eyras, Eduardo; Real, Francisco X.; Méndez, Raúl; Navarro, Pilar.

In: Nature Medicine, Vol. 18, No. 1, 01.2012, p. 83-90.

Research output: Contribution to journalArticle

Ortiz-Zapater, E, Pineda, D, Martínez-Bosch, N, Fernández-Miranda, G, Iglesias, M, Alameda, F, Moreno, M, Eliscovich, C, Eyras, E, Real, FX, Méndez, R & Navarro, P 2012, 'Key contribution of CPEB4mediated translational control to cancer progression', Nature Medicine, vol. 18, no. 1, pp. 83-90. https://doi.org/10.1038/nm.2540
Ortiz-Zapater E, Pineda D, Martínez-Bosch N, Fernández-Miranda G, Iglesias M, Alameda F et al. Key contribution of CPEB4mediated translational control to cancer progression. Nature Medicine. 2012 Jan;18(1):83-90. https://doi.org/10.1038/nm.2540
Ortiz-Zapater, Elena ; Pineda, David ; Martínez-Bosch, Neus ; Fernández-Miranda, Gonzalo ; Iglesias, Mar ; Alameda, Francesc ; Moreno, Mireia ; Eliscovich, Carolina ; Eyras, Eduardo ; Real, Francisco X. ; Méndez, Raúl ; Navarro, Pilar. / Key contribution of CPEB4mediated translational control to cancer progression. In: Nature Medicine. 2012 ; Vol. 18, No. 1. pp. 83-90.
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