title: CELF1 is a central node in post-transcriptional regulatory programmes underlying EMT.
abstract: The importance of translational regulation in tumour biology is increasingly appreciated. Here, we leverage polyribosomal profiling to prospectively define translational regulatory programs underlying epithelial-to-mesenchymal transition (EMT) in breast epithelial cells. We identify a group of ten translationally regulated drivers of EMT sharing a common GU-rich cis-element within the 3'-untranslated region (3'-UTR) of their mRNA. These cis-elements, necessary for the regulatory activity imparted by these 3'-UTRs, are directly bound by the CELF1 protein, which itself is regulated post-translationally during the EMT program. CELF1 is necessary and sufficient for both mesenchymal transition and metastatic colonization, and CELF1 protein, but not mRNA, is significantly overexpressed in human breast cancer tissues. Our data present an 11-component genetic pathway, invisible to transcriptional profiling approaches, in which the CELF1 protein functions as a central node controlling translational activation of genes driving EMT and ultimately tumour progression.
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030, USA.|Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Arindam
authors.initials: A
authors.lastname: Chaudhury
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Shebna
authors.initials: S
authors.lastname: Cheema
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030, USA.|Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Fachini
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030, USA.|Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Natee
authors.initials: N
authors.lastname: Kongchan
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030, USA.|Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Guojun
authors.initials: G
authors.lastname: Lu
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.|Department of Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Lukas M
authors.initials: LM
authors.lastname: Simon
authors.affiliation: Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Sufeng
authors.initials: S
authors.lastname: Mao
authors.affiliation: Department of Pathology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Rosen
authors.affiliation: Department of Pathology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Ittmann
authors.affiliation: Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA.|Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Susan G
authors.initials: SG
authors.lastname: Hilsenbeck
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Chad A
authors.initials: CA
authors.lastname: Shaw
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030, USA.|Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Joel R
authors.initials: JR
authors.lastname: Neilson
mesh_terms: D000818:Animals; D001943:Breast Neoplasms; D000067879:CELF1 Protein / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D004847:Epithelial Cells; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D053263:Gene Regulatory Networks; D006801:Humans; D051379:Mice; D009374:Neoplasms, Experimental; D011446:Prospective Studies; D040081:Protein Array Analysis; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D000067879:CELF1 Protein; C102843:CELF1 protein, human; D012333:RNA, Messenger