title: 3'-UTR-mediated post-transcriptional regulation of cancer metastasis: beginning at the end.
abstract: Epithelial-mesenchymal transition (EMT) and the underlying mechanisms and signaling pathways regulating such transitions have generated a lot of interest among cancer researchers. Much of this can be attributed to the apparent similarities in the molecular processes regulating embryonic EMT that can be recapitulated during tumor progression and metastasis. It appears that both embryonic and oncogenic EMT are regulated by an intricate interplay of transcriptional and post-transcriptional programs, and the recent discovery of a transcript-selective translational regulatory pathway controlling expression of EMT-associated mRNAs demonstrates the high fidelity and tight regulation associated with the process of EMT and metastatic progression. Heterogeneous nuclear ribonucleoprotein E1 (hnRNP E1) is emerging as a critical and integral modulator of TGFβ-induced EMT and subsequent tumor metastasis. Through its RNA-binding ability, hnRNP E1 binds distinct 3'-UTR structural elements present in mRNA transcripts required for EMT and translationally silences their expression. Translational silencing, mediated by hnRNP E1, occurs specifically at the translation elongation step through effects on the eukaryotic elongation factor-1 A1 (eEF1A1), and is relieved by Akt2-mediated phosphorylation. Interestingly, modulation of either the steady-state expression or the posttranscriptional modification of hnRNP E1 has a temporo-spatial effect on translational repression, tumorigenesis and cancer metastasis.
authors.affiliation: Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Arindam
authors.initials: A
authors.lastname: Chaudhury
authors.forename: George S
authors.initials: GS
authors.lastname: Hussey
authors.forename: Philip H
authors.initials: PH
authors.lastname: Howe
mesh_terms: D020413:3' Untranslated Regions; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009362:Neoplasm Metastasis / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D020648:Peptide Elongation Factor 1 / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C094814:EEF1A1 protein, human; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D020648:Peptide Elongation Factor 1; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; C494921:AKT2 protein, human; D051057:Proto-Oncogene Proteins c-akt