We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Alternative splicing of SYK regulates mitosis and cell survival.
- Authors
Prinos, Panagiotis; Garneau, Daniel; Lucier, Jean-François; Gendron, Daniel; Couture, Sonia; Boivin, Marianne; Brosseau, Jean-Philippe; Lapointe, Elvy; Thibault, Philippe; Durand, Mathieu; Tremblay, Karine; Gervais-Bird, Julien; Nwilati, Hanad; Klinck, Roscoe; Chabot, Benoit; Perreault, Jean-Pierre; Wellinger, Raymund J.; Elela, Sherif Abou
- 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.
- Subjects
GENES; MESSENGER RNA; RNA splicing; CANCER cells; APOPTOSIS; SPLEEN; PROTEIN-tyrosine kinases; MITOSIS
- Publication
Nature Structural & Molecular Biology, 2011, Vol 18, Issue 6, p673
- ISSN
1545-9993
- Publication type
Article
- DOI
10.1038/nsmb.2040