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.