The TWEAK-Fn14 cytokine-receptor axis: discovery, biology and therapeutic targeting

Nat Rev Drug Discov. 2008 May;7(5):411-25. doi: 10.1038/nrd2488.


TWEAK is a multifunctional cytokine that controls many cellular activities including proliferation, migration, differentiation, apoptosis, angiogenesis and inflammation. TWEAK acts by binding to Fn14, a highly inducible cell-surface receptor that is linked to several intracellular signalling pathways, including the nuclear factor-kappaB (NF-kappaB) pathway. The TWEAK-Fn14 axis normally regulates various physiological processes, in particular it seems to play an important, beneficial role in tissue repair following acute injury. Furthermore, recent studies have indicated that TWEAK-Fn14 axis signalling may contribute to cancer, chronic autoimmune diseases and acute ischaemic stroke. This Review provides an overview of TWEAK-Fn14 axis biology and summarizes the available data supporting the proposal that both TWEAK and Fn14 should be considered as potential targets for the development of novel therapeutics.

Publication types

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

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Humans
  • Neoplasms / therapy*
  • Receptors, Tumor Necrosis Factor / physiology*
  • Signal Transduction*
  • TWEAK Receptor


  • Cytokines
  • Receptors, Tumor Necrosis Factor
  • TNFRSF12A protein, human
  • TWEAK Receptor