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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Yu, Y; Suryo Rahmanto, Y; Lee, M-H; Wu, P-H; Phillip, JM; Huang, C-H; Vitolo, MI; Gaillard, S; Martin, SS; Wirtz, D; Shih, I-M; Wang, T-L

Published Date

  • July 2018

Published In

Volume / Issue

  • 37 / 28

Start / End Page

  • 3778 - 3789

PubMed ID

  • 29643476

Pubmed Central ID

  • 29643476

Electronic International Standard Serial Number (EISSN)

  • 1476-5594

International Standard Serial Number (ISSN)

  • 0950-9232

Digital Object Identifier (DOI)

  • 10.1038/s41388-018-0241-0

Language

  • eng