Alternative Splicing of SYK Regulates Mitosis and Cell Survival

Nat Struct Mol Biol. 2011 Jun;18(6):673-9. doi: 10.1038/nsmb.2040. Epub 2011 May 8.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing*
  • Apoptosis
  • Cell Line, Tumor
  • Cell Survival*
  • Epidermal Growth Factor / metabolism
  • Gene Expression Regulation*
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Mitosis*
  • Protein-Tyrosine Kinases / biosynthesis*
  • Protein-Tyrosine Kinases / genetics*
  • Syk Kinase


  • Intracellular Signaling Peptides and Proteins
  • Epidermal Growth Factor
  • Protein-Tyrosine Kinases
  • SYK protein, human
  • Syk Kinase