Recent insights into the actions of IGFBP-6
#MMPMID25808083
Bach LA
J Cell Commun Signal
2015[Jun]; 9
(2
): 189-200
PMID25808083
show ga
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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