Establishment of a TGFβ-Induced Post-Transcriptional EMT Gene Signature

• DOI: 10.1371/journal.pone.0052624
• Publication Date: 2012-12-20T17:39:57Z
• Authors: George S. Hussey; Laura A. Link; Andrew S. Brown; Breege V. Howley; Arindam Chaudhury; Philip H. Howe
• Keywords: Regulon; Proteome; YY1

A major challenge in the clinical management of human cancers is to accurately stratify patients according risk and likelihood a favorable response. Stratification confounded by significant phenotypic heterogeneity some tumor types, often without obvious criteria for subdivision. Despite intensive transcriptional array analyses, identity validation cancer specific 'signature genes' remains elusive, partially because transcriptome does not mirror proteome. The simplification associated with transcriptomic profiling take into consideration changes relative expression among transcripts that arise due post-transcriptional regulatory events. We have previously shown TGFβ post-transcriptionally regulates epithelial-mesenchymal transition (EMT) causing increased two transcripts, Dab2 ILEI, modulating hnRNP E1 phosphorylation. Using genome-wide combinatorial approach involving RIP-Chip analysis, we identified cohort translationally regulated mRNAs are induced during TGFβ-mediated EMT. Coordinated translational regulation constitutes regulon inhibiting related EMT-facilitating genes, thus enabling cell rapidly coordinately regulate multiple genes.