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Roles for neuregulins in human cancer

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Abstract

The human epidermal growth factor (EGF) receptor (HER) family of receptor tyrosine kinases has frequently been implicated in cancer. Apart from overexpression or mutation of these receptors, also the aberrant autocrine or paracrine activation of HERs by EGF-like ligands may be important in cancer progression. Neuregulins constitute a family of EGF-like ligands that bind to HER3 or HER4, preferably forming heterodimers with the orphan receptor HER2. Mesenchymal neuregulin typically serves as a pro-survival and pro-differentiation signal for adjacent epithelia. Disruption of the balance between proliferation and differentiation, because of autocrine production by the epithelial cells, increased sensitivity to paracrine signals or disruption of the spatial organization, may lead to constitutive receptor activation, in the absence of receptor overexpression. Consequently, the analysis of ligand expression and/or activated receptors in tumor samples may broaden the group of patients that can benefit from targeted therapies.

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Abbreviations

AMF:

autocrine motility factor

ARIA:

acetylcholine receptor-inducing activity

ATF4:

activating transcription factor 4

COX-2:

cyclooxygenase-2

EGF:

epidermal growth factor

E2:

estradiol

EF-1α:

elongation factor-1α

ER:

estrogen receptor

FAK:

focal adhesion kinase

G3BP:

GTPase-activating protein SH3 domain-binding protein

GADD153:

growth-arrest and DNA-damage 153

GAP:

GTPase-activating protein

GGF:

glial growth factor

HER:

human EGF-like receptor

HIF-1α:

hypoxia inducible factor-1α

hnRNP K:

heterogeneous nuclear ribonucleoprotein K

HRG:

heregulin

HSP70:

heat shock protein-70

IκB:

inhibitor of κB

MAPK/ERK:

mitogen-activated protein kinase/extracellular-regulated kinase

MMP:

matrix metalloproteinase

MMTV:

murine mammary tumor virus

MTA1:

metastasis and tumor-associated protein 1

NDF:

neu differentiation factor

NFκB:

nuclear factor κB

NRG:

neuregulin

Pak1:

p21-activated kinase 1

PGE2:

prostaglandin E2

PI3K:

phosphoinositide 3-kinase

PKB/Akt:

protein kinase B

PR:

progesterone receptor

RAFTK:

related adhesion focal tyrosine kinase

RARα:

retinoic acid receptor α

SMDF:

sensory and motor neuron-derived factor

uPA(R):

urokinase plasminogen activator (receptor)

VEGF:

vascular endothelial growth factor

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Authors and Affiliations

  1. Laboratory of Experimental Cancerology, Department of Radiotherapy and Nuclear Medicine, Ghent University Hospital, Ghent, Belgium

    Christophe Stove & Marc Bracke

  2. Units of Molecular Cell Biology and Molecular and Cellular Oncology, Department for Molecular Biomedical Research, VIB-Ghent University, Technologiepark 927, 9052, Zwijnaarde, Belgium

    Christophe Stove

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Stove, C., Bracke, M. Roles for neuregulins in human cancer. Clin Exp Metastasis 21, 665–684 (2005). https://doi.org/10.1007/s10585-004-6917-6

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