title: IGFBP-3: a cell fate pivot in cancer and disease.
abstract: One of the hallmarks in the advancement of cancer cells is an ability to overcome and acquire resistance to adverse conditions. There has been a large amount of cancer research on IGFBP-3 as a pro-apoptotic molecule in vitro. These pro-apoptotic properties, however, do not correlate with several studies linking high IGFBP-3 levels in breast cancer tissue to rapid growth and poor prognosis. Evidence is emerging that IGFBP-3 also exhibits pro-survival and growth-promoting properties in vitro. How IGFBP-3 pivots cell fate to either death or survival, it seems, comes down to a complex interplay between cells' microenvironments and the presence of cellular IGFBP-3 binding partners and growth factor receptors. The cytoprotective actions of IGFBP-3 are not restricted to cancer but are also observed in other disease states, such as retinopathy and brain ischaemia. Here we review the literature on this paradoxical nature of IGFBP-3, its pro-apoptotic and growth-inhibitory actions versus its cytoprotective and growth-potentiating properties, and discuss the implications of targeting IGFBP-3 for treatment of disease.
authors: Hormones and Cancer, Kolling Institute of Medical Research, The University of Sydney, Royal North Shore Hospital, St Leonards, NSW 2065, Australia.
authors: Michael A
authors: MA
authors: Johnson
authors: Hormones and Cancer, Kolling Institute of Medical Research, The University of Sydney, Royal North Shore Hospital, St Leonards, NSW 2065, Australia.
authors: Sue M
authors: SM
authors: Firth
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D004194:Disease / Q000235:genetics*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005812:Genes, Switch; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000502:physiology*; D009369:Neoplasms / Q000235:genetics*
chemical_list: C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3
keywords: Apoptosis; Autophagy; Cancer; Cell survival; IGFBP-3