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Ingermann, A.R., Yang, Y.F., Han, J., Mikami, A., Garza, A.E., Mohanraj, L., Fan, L., Idowu, M., Ware, J.L., Kim, H.S., Lee, D.Y. and Oh, Y. (2010) Identification of a Novel Cell Death Receptor Mediating IGFBP-3-Induced Anti-Tumor Effects in Breast and Prostate Cancer. Journal of Biological Chemistry, 285, 30233-30246. http://dx.doi.org/10.1074/jbc.M110.122226

has been cited by the following article:

• TITLE: Activation of Various Downstream Signaling Molecules by IGFBP-3

  AUTHORS: Hanief Mohammad Shahjee, Nisan Bhattacharyya

  KEYWORDS: Apoptosis, IGFBP-3, Stat-1, IGF-I, TGF-β

  JOURNAL NAME: Journal of Cancer Therapy, Vol.5 No.9, August 7, 2014

  ABSTRACT: Insulin-like growth factor binding protein-3 (IGFBP-3), a secretory protein, is the most abundant IGF binding protein present in human serum among all IGF binding proteins. IGFBP-3 shows decreased level of expression in cancerous cells but has been known to be present in significant amounts in normal or non-cancerous cells. IGFBP-3 can induce apoptosis in prostate cancer cells either in an IGF-dependent manner or independently of IGF binding. Although putative cell death specific Insulin-like growth factor binding protein-3 (IGFBP-3R) receptor(s) has recently been identified by which IGFBP-3 may induce its anti-tumor effects, IGFBP-3 has also been known to activate various downstream intracellular signaling molecules via a different mechanistic pathway. Stat-1 has been known to be one of the candidate molecules activated by IGFBP-3. IGFBP-3 can also inhibit Akt/IGF-1 survival pathway in MCF-7 breast cancer cells which ultimately leads to the induction of apoptosis in these cells. All these studies clearly demonstrate that IGFBP-3 regulates cell proliferation and promotes its pro-apoptotic effects in cancer cells in two different pathways: 1) sequester IGF-I to bind to IGF-I receptor to inhibit cell proliferation and induce apoptosis, 2) independent of IGF-I pathway, IGFBP-3 binds to some putative receptor and activate various downstream pro-apoptotic molecules involved in cell death.