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Making alternative splicing decisions during epithelial-to-mesenchymal transition (EMT)

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Abstract

Alternative splicing generates multiple mRNAs from a single transcript and is a major contributor to proteomic diversity and to the control of gene expression in complex organisms. Not surprisingly, this post-transcriptional event is tightly regulated in different tissues and developmental stages. An increasing body of evidences supports a causative role of aberrant alternative splicing in cancer. However, very little is known about its impact on cellular processes crucially involved in tumor progression. The aim of this review is to discuss the link between alternative splicing and the epithelial-to-mesenchymal transition (EMT), one of the major routes by which cancer cells acquire invasive capabilities and become metastatic. We begin with a brief overview of alternative splicing. Next, we discuss alternative splicing factors that regulate EMT. Finally, we provide examples of target genes presenting alternative splicing changes that contribute to the morphological conversions in the EMT process.

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Abbreviations

AS:

Alternative splicing

AS-NMD:

Alternative splicing-activated NMD

ECM:

Extracellular matrix

IDC:

Indole-derived compound

MMP:

Metalloproteinase

PTC:

Premature translation termination codon

NMD:

Nonsense-mediated RNA decay

ROS:

Reactive oxygen species

RTK:

Receptor tyrosine kinase

UTR:

Untranslated region

TOES:

Targeted oligonucleotide enhancers of splicing

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Acknowledgments

This work was supported by grants from the Associazione Italiana per la Ricerca sul Cancro (AIRC project number: 11913), the Association for International Cancer Research (AICR) to C.G. and grants from the Associazione Italiana per la Ricerca sul Cancro (AIRC), the Fondazione Cariplo and the European Union Network of Excellence on Alternative Splicing (EURASNET) to G.B.

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Correspondence to Giuseppe Biamonti or Claudia Ghigna.

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Biamonti, G., Bonomi, S., Gallo, S. et al. Making alternative splicing decisions during epithelial-to-mesenchymal transition (EMT). Cell. Mol. Life Sci. 69, 2515–2526 (2012). https://doi.org/10.1007/s00018-012-0931-7

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