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Recent insights into the actions of IGFBP-6

  • Research Article
  • Published:
Journal of Cell Communication and Signaling Aims and scope

Abstract

IGFBP-6 is an O-linked glycoprotein that preferentially binds IGF-II over IGF-I. It is a relatively selective inhibitor of IGF-II actions including proliferation, survival and differentiation of a wide range of cells. IGFBP-6 has recently been shown to have a number of IGF-independent actions, including promotion of apoptosis in some cells and inhibition of angiogenesis. IGFBP-6 also induces migration of tumour cells including rhabdomyosarcomas by an IGF-independent mechanism. This chemotactic effect is mediated by MAP kinases. IGFBP-6 binds to prohibitin-2 on the cell surface and the latter is required for IGFBP-6-induced migration by a mechanism that is independent of MAP kinases. IGFBP-6 may enter the nucleus and modulate cell survival and differentiation. IGFBP-6 expression is decreased in a number of cancer cells and it has been postulated to act as a tumour suppressor. IGFBP-6 expression is increased in a smaller number of cancers, which may reflect a compensatory mechanism to control IGF-II actions or IGF-independent actions. The relative balance of IGF-dependent and IGF-independent actions of IGFBP-6 in vivo together with the related question regarding the roles of IGFBP-6 binding to IGF and non-IGF ligands are keys to understanding the physiological role of this protein.

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Abbreviations

BAP:

B-cell receptor-associated protein

cAMP:

cyclic AMP

Hh:

hedgehog

HIF:

hypoxia-inducible factor

IGF:

insulin-like growth factor

IGFBP:

IGF binding protein

LMP:

LIM mineralization protein

MAP kinase:

mitogen activated protein kinase

MMP:

matrix metalloprotease

NF-κB:

nuclear factor-κB

PHB:

prohibitin

REA:

repressor of estrogen receptor activity

RMS:

rhabdomyosarcoma

SEMA:

semaphorin

TGF:

transforming growth factor

VEGF:

vascular endothelial growth factor

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Acknowledgements

The author’s work described in this review was funded by grants from the National Health and Medical Research Council of Australia, Australian Research Council, Cancer Council Victoria, Alfred Research Trust, Austin Hospital Medical Research Foundation and Melbourne Research Grants Scheme.

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  1. Department of Medicine (Alfred), Monash University, Prahran, 3181, Australia

    Leon A. Bach

  2. Department of Endocrinology and Diabetes, Alfred Hospital, Commercial Rd, Melbourne, 3004, Australia

    Leon A. Bach

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Bach, L.A. Recent insights into the actions of IGFBP-6. J. Cell Commun. Signal. 9, 189–200 (2015). https://doi.org/10.1007/s12079-015-0288-4

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