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IGFBP-2 - taking the lead in growth, metabolism and cancer

  • Steven W. Yau
  • Walid J. Azar
  • Matthew A. Sabin
  • George A. Werther
  • Vincenzo  C. Russo
REVIEW

Abstract

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.

Keywords

IGF system IGFBP-2 Growth Metabolism Obesity Diabetes Leukaemia Lung cancer Colon cancer 

Notes

Acknowledgments

This work was supported by the National Health and Medical Research Council (NHMRC) of Australia (Project Grant, # 1008062) awarded to GAW and VCR. MAS is supported through a National Health and Medical Research Council Professional Training Fellowship (APP1012201). SWY is a recipient of an Australian Postgraduate Award scholarship. We also wish to acknowledge the generous support from the Murdoch Childrens Research Institute and the Royal Children’s Hospital Foundation to GAW, MAS and VCR. We also like to thank the Victorian Government Operational Infrastructure Support Program.

Disclosure statement

This work was supported by the National Health and Medical Research Council (NHMRC) of Australia (Project Grant, # 1008062) awarded to GAW, VCR, and by the Victorian Government Operational Infrastructure Support Program. SWY is a recipient of an Australian Postgraduate Award scholarship.

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Copyright information

© The International CCN Society 2015

Authors and Affiliations

  • Steven W. Yau
    • 1
    • 2
  • Walid J. Azar
    • 3
  • Matthew A. Sabin
    • 1
    • 2
  • George A. Werther
    • 1
    • 2
  • Vincenzo  C. Russo
    • 1
    • 2
    • 4
  1. 1.Deparment of Cell Biology, Hormone Research, Murdoch Childrens Research InstituteRoyal Children’s HospitalParkvilleAustralia
  2. 2.Department of PaediatricsUniversity of MelbourneParkvilleAustralia
  3. 3.Department of Cancer Genomics and Biochemistry, Cancer ResearchPeter MacCallum Cancer CentreMelbourneAustralia
  4. 4.Cell Biology, Murdoch Childrens Research InstituteRoyal Children’s HospitalParkvilleAustralia

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