{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T07:15:44Z","timestamp":1773299744043,"version":"3.50.1"},"reference-count":124,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2017,12,29]],"date-time":"2017-12-29T00:00:00Z","timestamp":1514505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/genes9010009","type":"journal-article","created":{"date-parts":[[2017,12,29]],"date-time":"2017-12-29T10:58:47Z","timestamp":1514545127000},"page":"9","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Signaling Pathways Driving Aberrant Splicing in Cancer Cells"],"prefix":"10.3390","volume":"9","author":[{"given":"V\u00e2nia","family":"Gon\u00e7alves","sequence":"first","affiliation":[{"name":"Department of Human Genetics, Instituto Nacional de Sa\u00fade Doutor Ricardo Jorge, Avenida Padre Cruz, 1649-016 Lisboa, Portugal"},{"name":"BioISI\u2014Biosystems &amp; Integrative Sciences Institute, Faculty of Sciences, University of Lisbon, 1649-004 Lisboa, Portugal"}]},{"given":"Joana","family":"Pereira","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Instituto Nacional de Sa\u00fade Doutor Ricardo Jorge, Avenida Padre Cruz, 1649-016 Lisboa, Portugal"},{"name":"BioISI\u2014Biosystems &amp; Integrative Sciences Institute, Faculty of Sciences, University of Lisbon, 1649-004 Lisboa, Portugal"}]},{"given":"Peter","family":"Jordan","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Instituto Nacional de Sa\u00fade Doutor Ricardo Jorge, Avenida Padre Cruz, 1649-016 Lisboa, Portugal"},{"name":"BioISI\u2014Biosystems &amp; Integrative Sciences Institute, Faculty of Sciences, University of Lisbon, 1649-004 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2017,12,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/nrm3742","article-title":"A day in the life of the spliceosome","volume":"15","author":"Matera","year":"2014","journal-title":"Nat. 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