Inhibition of ovarian tumor cell invasiveness by targeting SYK in the tyrosine kinase signaling pathway

Oncogene. 2018 Jul;37(28):3778-3789. doi: 10.1038/s41388-018-0241-0. Epub 2018 Apr 11.


Cell motility and invasiveness are prerequisites for dissemination, and largely account for cancer mortality. We have identified an actionable kinase, spleen tyrosine kinase (SYK), which is keenly tightly associated with tumor progression in ovarian cancer. Here, we report that active recombinant SYK directly phosphorylates cortactin and cofilin, which are critically involved in assembly and dynamics of actin filament through phosphorylation signaling. Enhancing SYK activity by inducing expression of a constitutively active SYK mutant, SYK130E, increased growth factor-stimulated migration and invasion of ovarian cancer cells, which was abrogated by cortactin knockdown. Similarly, SYK inhibitors significantly decreased invasion of ovarian cancer cells across basement membrane in real-time transwell assays and in 3D tumor spheroid models. SYK inactivation by targeted gene knockout or by small molecule inhibition reduced actin polymerization. Collectively, this study reported a new mechanism by which SYK signaling regulates ovarian cancer cell motility and invasiveness, and suggest a target-based strategy to prevent or suppress the advancement of ovarian malignancies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basement Membrane / drug effects
  • Basement Membrane / metabolism
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Humans
  • Neoplasm Invasiveness / pathology*
  • Phosphorylation / drug effects
  • Signal Transduction / drug effects*
  • Syk Kinase / metabolism*


  • SYK protein, human
  • Syk Kinase