IGF-I mediated survival pathways in normal and malignant cells.
The type-I and -II insulin-like growth factors (IGF-I, II) are now established as survival- or proliferation-factors in many in vitro systems. Of note IGFs provide trophic support for multiple cell types or organ cultures explanted from various species, and delay the onset of programmed cell death (apoptosis) through the mitochondrial (intrinsic pathway) or by antagonizing activation of cytotoxic cytokine signaling (extrinsic pathway). In some instances, IGFs protect against other forms of death such as necrosis or autophagy. The effect of IGFs on cell survival appears to be context specific, being determined both by the cell origin (tissue specific) and the cellular stress that induces loss of cellular viability. In many human cancers, there is a strong association with dysregulated IGF signaling, and this association has been extensively reviewed recently. IGF-regulation is also disrupted in childhood cancers as a consequence of chromosomal translocations. IGFs are implicated also in acute renal failure, traumatic injury to brain tissue, and cardiac disease. This article focuses on the role of IGFs and their cellular signaling pathways that provide survival signals in stressed cells.
Kurmasheva
Raushan T
RT
Department of Molecular Pharmacology, St. Jude Children's Research Hospital, 332 N. Lauderdale St., Memphis, TN 38105-2794, USA.
Houghton
Peter J
PJ
D000818:Animals; D017209:Apoptosis; D002470:Cell Survival; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008928:Mitochondria / Q000502:physiology; D009369:Neoplasms / Q000473:pathology*; D017526:Receptor, IGF Type 1 / Q000502:physiology*; D015398:Signal Transduction
D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1