Cellular FLICE-inhibitory protein (c-FLIP) signalling: a key regulator of receptor-mediated apoptosis in physiologic context and in cancer

Int J Biochem Cell Biol. 2010 Feb;42(2):210-3. doi: 10.1016/j.biocel.2009.11.015. Epub 2009 Nov 22.


Cellular FLICE-inhibitory protein (c-FLIP) is a catalytically inactive procaspase-8/10 homologue that associates with the signalling complex downstream of death-receptors negatively interfering with apoptotic signalling. Three c-FLIP splice variants have been identified: c-FLIP(L), c-FLIP(S) and c-FLIP(R), with all three functioning as apoptosis inhibitors involved in modulation of caspase-8/10 activity in both physiologic and pathologic contexts. Furthermore, a cell-type specific pro-apoptotic role, depending on caspase-8 to c-FLIP(L) ratio, has also been described for the long isoform. The present review summarizes recent findings concerning c-FLIP proteins' function and regulation, with a main focus on the c-FLIP(L) deregulated expression in cancer. The role of c-FLIP(L) as anti-apoptotic pro-survival factor in tumors and the potential utility of this molecule as a possible alternative therapeutic target are discussed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Apoptosis* / drug effects
  • CASP8 and FADD-Like Apoptosis Regulating Protein / metabolism*
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms / metabolism*
  • Neoplasms / pathology*
  • Signal Transduction* / drug effects


  • Antineoplastic Agents
  • CASP8 and FADD-Like Apoptosis Regulating Protein