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Signaling Pathways Driving Aberrant Splicing in Cancer Cells

Department of Human Genetics, Instituto Nacional de Saúde Doutor Ricardo Jorge, Avenida Padre Cruz, 1649-016 Lisboa, Portugal
BioISI—Biosystems & Integrative Sciences Institute, Faculty of Sciences, University of Lisbon, 1649-004 Lisboa, Portugal
Author to whom correspondence should be addressed.
Received: 6 November 2017 / Revised: 7 December 2017 / Accepted: 18 December 2017 / Published: 29 December 2017
(This article belongs to the Special Issue Aberrant Pre-mRNA Splicing in Disease)
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Aberrant profiles of pre-mRNA splicing are frequently observed in cancer. At the molecular level, an altered profile results from a complex interplay between chromatin modifications, the transcriptional elongation rate of RNA polymerase, and effective binding of the spliceosome to the generated transcripts. Key players in this interplay are regulatory splicing factors (SFs) that bind to gene-specific splice-regulatory sequence elements. Although mutations in genes of some SFs were described, a major driver of aberrant splicing profiles is oncogenic signal transduction pathways. Signaling can affect either the transcriptional expression levels of SFs or the post-translational modification of SF proteins, and both modulate the ratio of nuclear versus cytoplasmic SFs in a given cell. Here, we will review currently known mechanisms by which cancer cell signaling, including the mitogen-activated protein kinases (MAPK), phosphatidylinositol 3 (PI3)-kinase pathway (PI3K) and wingless (Wnt) pathways but also signals from the tumor microenvironment, modulate the activity or subcellular localization of the Ser/Arg rich (SR) proteins and heterogeneous nuclear ribonucleoproteins (hnRNPs) families of SFs. View Full-Text
Keywords: alternative splicing; cancer cell; genetic program; signaling pathway; tumorigenesis; tumor microenvironment alternative splicing; cancer cell; genetic program; signaling pathway; tumorigenesis; tumor microenvironment

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Gonçalves, V.; Pereira, J.F.S.; Jordan, P. Signaling Pathways Driving Aberrant Splicing in Cancer Cells. Genes 2018, 9, 9.

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