C-FLIP promotes the motility of cancer cells by activating FAK and ERK, and increasing MMP-9 expression

Deokbum Park, Eunsook Shim, Youngmi Kim, Young Myeong Kim, Hansoo Lee, Jongseon Choe, Dongmin Kang, Yun Sil Lee, Dooil Jeoung

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

We examined the role of c-FLIP in the motility of HeLa cells. A small interfering RNA (siRNA directed against c-FLIP inhibited the adhesion and motility of the cells without affecting their growth rate. The long form of c-FLIP (c-FLIPL), but not the short form (c-FLIPs), enhanced adhesion and motility. Downregulation of c-FLIPL -with siRNA decreased phosphorylation of FAK and ERK, while overexpression of c-FLIP, increased their phosphorylation. Overexpression of FAK activated ERK, and enhanced the motility of HeLa cells. FRNK, an inhibitory fragment of FAK, inhibited ERK and decreased motility. Inhibition of ERK also significantly suppressed c-FLIPL-promoted motility. Inhibition of ROCK by Y27632 suppressed the c-FLIPL-promoted motility by reducing phosphorylalion of FAK in ERK. Overexpression of c-FLIPL increased the expression and secretion of MMP-9, and inhibition of MMP-9 by Iloniaslat reduced c-FLIPL- promoted cell motilily. A caspase-like domain (amino acids 222-376) was found to be necessary for the c-FLIPL-promoted cell motility. We conclude that c-FLIPL promotes the motility of HeLa cells by activating FAK and ERK, and increasing MMP-9 expression.

Original languageEnglish
Pages (from-to)184-195
Number of pages12
JournalMolecules and Cells
Volume25
Issue number2
StatePublished - 30 Apr 2008

Keywords

  • C-FLIP
  • ERK
  • FAK
  • MMP-9
  • Motility

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