Posttranscriptional regulation by RNA-binding proteins during epithelial-to-mesenchymal transition
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Cellular and Molecular Life Sciences
Review
Posttranscriptional regulation by RNA‑binding proteins during epithelial‑to‑mesenchymal transition Luis A. Aparicio · Vanessa Abella · Manuel Valladares · Angélica Figueroa
Received: 27 March 2013 / Revised: 10 May 2013 / Accepted: 16 May 2013 © The Author(s) 2013. This article is published with open access at Springerlink.com
Abstract Epithelial-to-mesenchymal transition (EMT), one of the crucial steps for carcinoma cells to acquire invasive capacity, results from the disruption of cell–cell contacts and the acquisition of a motile mesenchymal phenotype. Although the transcriptional events controlling EMT have been extensively studied, in recent years, several posttranscriptional mechanisms have emerged as critical in the regulation of EMT during tumor progression. In this review, we highlight the regulation of posttranscriptional events in EMT by RNA-binding proteins (RBPs). RBPs are responsible for controlling pre-mRNA splicing, capping, and polyadenylation, as well as mRNA export, turnover, localization, and translation. We discuss the most relevant aspects of RBPs controlling the metabolism of EMTrelated mRNAs, and describe the implication of novel posttranscriptional mechanisms regulating EMT in response to different signaling pathways. Novel insight into posttranscriptional regulation of EMT by RBPs is uncovering new therapeutic targets in cancer invasion and metastasis. Keywords Epithelial-to-mesenchymal transition · Tumor progression · Posttranscriptional regulation · RNA-binding proteins
L. A. Aparicio · M. Valladares Servizo de Oncología Médica, Complejo Hospitalario Universitario A Coruña (CHUAC), SERGAS, A Coruña, Spain V. Abella · A. Figueroa (*) Translational Cancer Research Group, Instituto de Investigación Biomédica A Coruña (INIBIC), Complejo Hospitalario Universitario A Coruña (CHUAC), SERGAS, Xubias de Arriba 84, 15006 A Coruña, Spain e-mail: angelica.figueroa.conde‑[email protected]
Abbreviations AJs Adherens junctions AREs AU-rich elements AS-NMD Activated-splicing nonsense-mediated decay BAT TGF-Beta-activated translation CD44 Cluster of differentiation 44 CD44s Cluster of differentiation 44 standard isoform CD44v Cluster of differentiation 44 variable isoform ECM Extracellular matrix eEF1A1 Eukaryotic elongation factor-1 A1 ELAV Embryonic lethal abnormal vision EMT Epithelial-to-mesenchymal transition ENAH Enable homolog ESRPs Epithelial splicing regulatory proteins FGF2 Fibroblast growth factor 2 FGFR2 Fibroblast growth factor receptor 2 HnRNPs Heterogeneous ribonucleoprotein particles HuR Human antigen R ILEI Interleukin-like EMT inducer LKB1 Liver kinase B1 NF2 Neurofibromatosis type II tumor suppression protein NMD Nonsense-mediated mRNA decay PAI-RBP1 Plasminogen activator inhibitor 1-RNA binding protein PCBP1 Poly(rC)-binding protein 1 PI3K Phosphatidylinositide 3-kinase PRL-3 Phosphatase of regenerating liver 3 PSF Polypyrimidine tract-binding proteinassociated splicing factor PTB Phosphotyrosine-binding RB
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