Leukemia inhibitory factor (LIF)

Cytokine Growth Factor Rev. 2015 Oct;26(5):533-44. doi: 10.1016/j.cytogfr.2015.07.001. Epub 2015 Jul 4.


Leukemia inhibitory factor (LIF) is the most pleiotropic member of the interleukin-6 family of cytokines. It utilises a receptor that consists of the LIF receptor β and gp130 and this receptor complex is also used by ciliary neurotrophic growth factor (CNTF), oncostatin M, cardiotrophin1 (CT1) and cardiotrophin-like cytokine (CLC). Despite common signal transduction mechanisms (JAK/STAT, MAPK and PI3K) LIF can have paradoxically opposite effects in different cell types including stimulating or inhibiting each of cell proliferation, differentiation and survival. While LIF can act on a wide range of cell types, LIF knockout mice have revealed that many of these actions are not apparent during ordinary development and that they may be the result of induced LIF expression during tissue damage or injury. Nevertheless LIF does appear to have non-redundant actions in maternal receptivity to blastocyst implantation, placental formation and in the development of the nervous system. LIF has also found practical use in the maintenance of self-renewal and totipotency of embryonic stem cells and induced pluripotent stem cells.

Keywords: Embryonic stem cells; JAK/STAT/SOCS; LIF receptor; Leukemia inhibitory factor; Nerve and muscle; Pregnancy.

Publication types

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

MeSH terms

  • Animals
  • Blastocyst / immunology
  • Cytokine Receptor gp130 / genetics
  • Cytokine Receptor gp130 / immunology
  • Embryo Implantation / genetics
  • Embryo Implantation / immunology
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / immunology
  • Human Embryonic Stem Cells / immunology
  • Humans
  • Janus Kinases / genetics
  • Janus Kinases / immunology
  • Leukemia Inhibitory Factor / genetics
  • Leukemia Inhibitory Factor / immunology*
  • MAP Kinase Signaling System / genetics
  • MAP Kinase Signaling System / immunology*
  • Mice
  • Mice, Knockout
  • Mouse Embryonic Stem Cells / immunology
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / immunology
  • Receptors, OSM-LIF / genetics
  • Receptors, OSM-LIF / immunology
  • STAT Transcription Factors / genetics
  • STAT Transcription Factors / immunology


  • IL6ST protein, human
  • LIF protein, human
  • Leukemia Inhibitory Factor
  • Lif protein, mouse
  • Receptors, OSM-LIF
  • STAT Transcription Factors
  • Cytokine Receptor gp130
  • Phosphatidylinositol 3-Kinases
  • Janus Kinases