title: Key contribution of CPEB4-mediated translational control to cancer progression.
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.
authors.affiliation: Cancer Research Programme, Hospital del Mar Research Institute (IMIM), Barcelona, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Ortiz-Zapater
authors.forename: David
authors.initials: D
authors.lastname: Pineda
authors.forename: Neus
authors.initials: N
authors.lastname: Martínez-Bosch
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Fernández-Miranda
authors.forename: Mar
authors.initials: M
authors.lastname: Iglesias
authors.forename: Francesc
authors.initials: F
authors.lastname: Alameda
authors.forename: Mireia
authors.initials: M
authors.lastname: Moreno
authors.forename: Carolina
authors.initials: C
authors.lastname: Eliscovich
authors.forename: Eduardo
authors.initials: E
authors.lastname: Eyras
authors.forename: Francisco X
authors.initials: FX
authors.lastname: Real
authors.forename: Raúl
authors.initials: R
authors.lastname: Méndez
authors.forename: Pilar
authors.initials: P
authors.lastname: Navarro
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply / Q000235:genetics / Q000473:pathology*; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000098:blood supply / Q000235:genetics / Q000473:pathology*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000235:genetics; D010183:Pancreatic Ducts / Q000098:blood supply / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000098:blood supply / Q000235:genetics / Q000473:pathology*; D026723:Polyadenylation; D014176:Protein Biosynthesis / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C554939:CPEB4 protein, human; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins