title: Establishment of a TGFβ-induced post-transcriptional EMT gene signature.
abstract: A major challenge in the clinical management of human cancers is to accurately stratify patients according to risk and likelihood of a favorable response. Stratification is confounded by significant phenotypic heterogeneity in some tumor types, often without obvious criteria for subdivision. Despite intensive transcriptional array analyses, the identity and validation of cancer specific 'signature genes' remains elusive, partially because the transcriptome does not mirror the proteome. The simplification associated with transcriptomic profiling does not take into consideration changes in the relative expression among transcripts that arise due to post-transcriptional regulatory events. We have previously shown that TGFβ post-transcriptionally regulates epithelial-mesenchymal transition (EMT) by causing increased expression of two transcripts, Dab2 and ILEI, by modulating hnRNP E1 phosphorylation. Using a genome-wide combinatorial approach involving expression profiling and RIP-Chip analysis, we have identified a cohort of translationally regulated mRNAs that are induced during TGFβ-mediated EMT. Coordinated translational regulation by hnRNP E1 constitutes a post-transcriptional regulon inhibiting the expression of related EMT-facilitating genes, thus enabling the cell to rapidly and coordinately regulate multiple EMT-facilitating genes.
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: George S
authors.initials: GS
authors.lastname: Hussey
authors.forename: Laura A
authors.initials: LA
authors.lastname: Link
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Brown
authors.forename: Breege V
authors.initials: BV
authors.lastname: Howley
authors.forename: Arindam
authors.initials: A
authors.lastname: Chaudhury
authors.forename: Philip H
authors.initials: PH
authors.lastname: Howe
mesh_terms: D000818:Animals; D001483:Base Sequence; D016000:Cluster Analysis; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000378:metabolism; D051379:Mice; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D014176:Protein Biosynthesis; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects*; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D020218:Response Elements; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D034441:Heterogeneous-Nuclear Ribonucleoproteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta