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Statements

Subject Item
n2:RIV%2F00209805%3A_____%2F13%3A%230000413%21RIV14-GA0-00209805
rdf:type
n3:Vysledek skos:Concept
rdfs:seeAlso
http://www.nature.com/onc/journal/v32/n20/full/onc2012346a.html
dcterms:description
Clinical studies have defined the core 'genetic blueprint' of a cancer cell, but this information does not necessarily predict the cancer phenotype. Signalling hubs that mediate such phenotype have been identified largely using OMICS platforms that measure dynamic molecular changes within the cancer cell landscape. The pro-oncogenic protein anterior gradient 2 (AGR2) is a case in point; AGR2 has been shown using a range of expression platforms to be involved in asthma, inflammatory bowel disease, cell transformation, cancer drug resistance and metastatic growth. AGR2 protein is also highly overexpressed in a diverse range of human cancers and can be secreted and detected in extracellular fluids, thus representing a compelling pro-oncogenic signalling intermediate in human cancer. AGR2 belongs to the protein disulphide isomerase family with all the key features of an endoplasmic reticulum-resident protein-this gives clues into how it might function as an oncoprotein through the regulation of protein folding, maturation and secretion that can drive metastatic cell growth. In this review, we will describe the known aspects of AGR2 molecular biology, including gene structure and regulation, emerging protein interaction networks and how its subcellular localization mediates its biological functions. We will finally review the cases of AGR2 expression in human cancers, the pathophysiological consequences of AGR2 overexpression, its potential role as a tumour biomarker that predicts the response to therapy and how the AGR2 pathway might form the basis for drug discovery programmes aimed at targeting protein folding/maturation pathways that mediate secretion and metastasis. Clinical studies have defined the core 'genetic blueprint' of a cancer cell, but this information does not necessarily predict the cancer phenotype. Signalling hubs that mediate such phenotype have been identified largely using OMICS platforms that measure dynamic molecular changes within the cancer cell landscape. The pro-oncogenic protein anterior gradient 2 (AGR2) is a case in point; AGR2 has been shown using a range of expression platforms to be involved in asthma, inflammatory bowel disease, cell transformation, cancer drug resistance and metastatic growth. AGR2 protein is also highly overexpressed in a diverse range of human cancers and can be secreted and detected in extracellular fluids, thus representing a compelling pro-oncogenic signalling intermediate in human cancer. AGR2 belongs to the protein disulphide isomerase family with all the key features of an endoplasmic reticulum-resident protein-this gives clues into how it might function as an oncoprotein through the regulation of protein folding, maturation and secretion that can drive metastatic cell growth. In this review, we will describe the known aspects of AGR2 molecular biology, including gene structure and regulation, emerging protein interaction networks and how its subcellular localization mediates its biological functions. We will finally review the cases of AGR2 expression in human cancers, the pathophysiological consequences of AGR2 overexpression, its potential role as a tumour biomarker that predicts the response to therapy and how the AGR2 pathway might form the basis for drug discovery programmes aimed at targeting protein folding/maturation pathways that mediate secretion and metastasis.
dcterms:title
Emerging roles for the pro-oncogenic anterior gradient-2 in cancer development Emerging roles for the pro-oncogenic anterior gradient-2 in cancer development
skos:prefLabel
Emerging roles for the pro-oncogenic anterior gradient-2 in cancer development Emerging roles for the pro-oncogenic anterior gradient-2 in cancer development
skos:notation
RIV/00209805:_____/13:#0000413!RIV14-GA0-00209805
n3:predkladatel
n4:ico%3A00209805
n5:aktivita
n12:P
n5:aktivity
P(ED2.1.00/03.0101), P(GAP301/10/1615), P(NT13794)
n5:cisloPeriodika
20
n5:dodaniDat
n14:2014
n5:domaciTvurceVysledku
n11:9637419 n11:1330586 Murray, Euan
n5:druhVysledku
n8:J
n5:duvernostUdaju
n16:S
n5:entitaPredkladatele
n15:predkladatel
n5:idSjednocenehoVysledku
72653
n5:idVysledku
RIV/00209805:_____/13:#0000413
n5:jazykVysledku
n19:eng
n5:klicovaSlova
AGR2; PDI; endoplasmic reticulum; secretome; p53; tumour
n5:klicoveSlovo
n6:AGR2 n6:tumour n6:secretome n6:PDI n6:endoplasmic%20reticulum n6:p53
n5:kodStatuVydavatele
GB - Spojené království Velké Británie a Severního Irska
n5:kontrolniKodProRIV
[63F153E726C4]
n5:nazevZdroje
Oncogene
n5:obor
n20:FD
n5:pocetDomacichTvurcuVysledku
3
n5:pocetTvurcuVysledku
9
n5:projekt
n18:NT13794 n18:ED2.1.00%2F03.0101 n18:GAP301%2F10%2F1615
n5:rokUplatneniVysledku
n14:2013
n5:svazekPeriodika
32
n5:tvurceVysledku
Vojtěšek, Bořivoj Murray, Euan Hrstka, Roman
n5:wos
000319274300001
s:issn
0950-9232
s:numberOfPages
11
n13:doi
10.1038/onc.2012.346