Sci. Signal., 18 December 2012
Deadly Receptor BlockadeWhen bound to insulin-like growth factor 1 or 2 (IGF-1/2), the IGF-1 receptor (IGF1R) promotes protein synthesis, cell growth, and survival. One mechanism by which the family of IGF-binding proteins (IGFBPs) interferes with IGF1R activation is by binding to IGF-1/2. Evdokimova et al. showed that, unlike other IGFBPs, IGFBP7 attenuated activation of IGF1R in various cell lines by interacting with the extracellular domain of IGF1R and preventing IGF-1/2 from binding to the receptor. IGFBP7 increased the abundance of IGF1R in various normal and cancer cells and xenograft tumors. However, in cultured cells, IGFBP7 treatment resulted in the retention of IGF1R at the cell surface in an inactive form and in apoptosis. Thus, IGFBP7 could be used to trigger cell death in tumors that depend on IGF-1/2 for growth or survival.
Citation: V. Evdokimova, C. E. Tognon, T. Benatar, W. Yang, K. Krutikov, M. Pollak, P. H. B. Sorensen, A. Seth, IGFBP7 Binds to the IGF-1 Receptor and Blocks Its Activation by Insulin-Like Growth Factors. Sci. Signal. 5, ra92 (2012).
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