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Updated: Apr 27, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
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IGFBP-3: a cell fate pivot in cancer and disease
Michael A Johnson1, Sue M Firth1
1Hormones and Cancer, Kolling Institute of Medical Research, The University of Sydney, Royal North Shore Hospital, St Leonards, NSW 2065, Australia.
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.
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