title: Alternative splicing of SYK regulates mitosis and cell survival.
abstract: Most human genes produce multiple mRNA isoforms through alternative splicing. However, the biological relevance of most splice variants remains unclear. In this study, we evaluated the functional impact of alternative splicing in cancer cells. We modulated the splicing pattern of 41 cancer-associated splicing events and scored the effects on cell growth, viability and apoptosis, identifying three isoforms essential for cell survival. Specifically, changing the splicing pattern of the spleen tyrosine kinase gene (SYK) impaired cell-cycle progression and anchorage-independent growth. Notably, exposure of cancer cells to epithelial growth factor modulated the SYK splicing pattern to promote the pro-survival isoform that is associated with cancer tissues in vivo. The data suggest that splicing of selected genes is specifically modified during tumor development to allow the expression of isoforms that promote cancer cell survival.
authors.affiliation: Laboratoire de Génomique Fonctionnelle, Université de Sherbrooke, Sherbrooke, Québec, Canada.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Prinos
authors.forename: Daniel
authors.initials: D
authors.lastname: Garneau
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Lucier
authors.forename: Daniel
authors.initials: D
authors.lastname: Gendron
authors.forename: Sonia
authors.initials: S
authors.lastname: Couture
authors.forename: Marianne
authors.initials: M
authors.lastname: Boivin
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Brosseau
authors.forename: Elvy
authors.initials: E
authors.lastname: Lapointe
authors.forename: Philippe
authors.initials: P
authors.lastname: Thibault
authors.forename: Mathieu
authors.initials: M
authors.lastname: Durand
authors.forename: Karine
authors.initials: K
authors.lastname: Tremblay
authors.forename: Julien
authors.initials: J
authors.lastname: Gervais-Bird
authors.forename: Hanad
authors.initials: H
authors.lastname: Nwilati
authors.forename: Roscoe
authors.initials: R
authors.lastname: Klinck
authors.forename: Benoit
authors.initials: B
authors.lastname: Chabot
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Perreault
authors.forename: Raymund J
authors.initials: RJ
authors.lastname: Wellinger
authors.forename: Sherif Abou
authors.initials: SA
authors.lastname: Elela
mesh_terms: D017398:Alternative Splicing; D017209:Apoptosis; D045744:Cell Line, Tumor; D002470:Cell Survival; D004815:Epidermal Growth Factor / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008938:Mitosis; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics*; D000072377:Syk Kinase
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D004815:Epidermal Growth Factor; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase