Open AccessIGFBP‐2 ‐ taking the lead in growth, metabolism and cancer
Author(s) -
Yau Steven W.,
Azar Walid J.,
Sabin Matthew A.,
Werther George A.,
Russo Vincenzo C.
Publication year - 2015
Publication title -
journal of cell communication and signaling
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 44
eISSN - 1873-961X
pISSN - 1873-9601
DOI - 10.1007/s12079-015-0261-2
Subject(s) - extracellular matrix , receptor , adipogenesis , microbiology and biotechnology , cell growth , insulin like growth factor binding protein , biology , cell surface receptor , cancer cell , integrin , chemistry , in vitro , growth factor , cancer research , cancer , medicine , insulin like growth factor , biochemistry
The activity of the Insulin‐like Growth Factors (IGFs) ligands elicited via their receptors and transduced by various intracellular signal pathways is modulated by the IGF Binding Proteins (IGFBPs). Among all the IGFBPs, IGFBP‐2 has been implicated in the regulation of IGF activity in most tissue and organs. Besides binding to IGFs in the circulation these IGF‐regulatory activities of IGFBP‐2 involve interactions with components of the extracellular matrix, cell surface proteoglycans and integrin receptors. In addition to these local peri‐cellular activities, IGFBP‐2 exerts other key functions within the nucleus, where IGFBP‐2 directly or indirectly promotes transcriptional activation of specific genes. All of these IGFBP‐2 activities, intrinsic or dependent on IGFs, contribute to its functional roles in growth/development, metabolism and malignancy as evidenced by studies in IGFBP‐2 animal models and also by many in vitro studies. Finally, preclinical studies have demonstrated that IGFBP‐2 administration can be beneficial in improving metabolic responses (inhibition of adipogenesis and enhanced insulin sensitivity), while blockade of IGFBP‐2 appears to be an effective approach to inhibiting tumour growth and metastasis.