Secretion of protein disulphide isomerase AGR2 confers tumorigenic properties

The extracellular matrix (ECM) plays an instrumental role in determining the spatial orientation of epithelial polarity and the formation of lumens in glandular tissues during morphogenesis. Here, we show that the Endoplasmic Reticulum (ER)-resident protein anterior gradient-2 (AGR2), a soluble prot...

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Main Authors:	Fessart, Delphine, Domblides, Charlotte, Avril, Tony, Eriksson, Leif A, Begueret, Hugues, Pineau, Raphael, Malrieux, Camille, Dugot-Senant, Nathalie, Lucchesi, Carlo, Chevet, Eric, Delom, Frederic
Format:	Online
Language:	English
Published:	eLife Sciences Publications, Ltd 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4940162/

id	pubmed-4940162
recordtype	oai_dc
spelling	pubmed-49401622016-07-13 Secretion of protein disulphide isomerase AGR2 confers tumorigenic properties Fessart, Delphine Domblides, Charlotte Avril, Tony Eriksson, Leif A Begueret, Hugues Pineau, Raphael Malrieux, Camille Dugot-Senant, Nathalie Lucchesi, Carlo Chevet, Eric Delom, Frederic Cancer Biology The extracellular matrix (ECM) plays an instrumental role in determining the spatial orientation of epithelial polarity and the formation of lumens in glandular tissues during morphogenesis. Here, we show that the Endoplasmic Reticulum (ER)-resident protein anterior gradient-2 (AGR2), a soluble protein-disulfide isomerase involved in ER protein folding and quality control, is secreted and interacts with the ECM. Extracellular AGR2 (eAGR2) is a microenvironmental regulator of epithelial tissue architecture, which plays a role in the preneoplastic phenotype and contributes to epithelial tumorigenicity. Indeed, eAGR2, is secreted as a functionally active protein independently of its thioredoxin-like domain (CXXS) and of its ER-retention domain (KTEL), and is sufficient, by itself, to promote the acquisition of invasive and metastatic features. Therefore, we conclude that eAGR2 plays an extracellular role independent of its ER function and we elucidate this gain-of-function as a novel and unexpected critical ECM microenvironmental pro-oncogenic regulator of epithelial morphogenesis and tumorigenesis. eLife Sciences Publications, Ltd 2016-05-30 /pmc/articles/PMC4940162/ /pubmed/27240165 http://dx.doi.org/10.7554/eLife.13887 Text en © 2016, Fessart et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Fessart, Delphine Domblides, Charlotte Avril, Tony Eriksson, Leif A Begueret, Hugues Pineau, Raphael Malrieux, Camille Dugot-Senant, Nathalie Lucchesi, Carlo Chevet, Eric Delom, Frederic
spellingShingle	Fessart, Delphine Domblides, Charlotte Avril, Tony Eriksson, Leif A Begueret, Hugues Pineau, Raphael Malrieux, Camille Dugot-Senant, Nathalie Lucchesi, Carlo Chevet, Eric Delom, Frederic Secretion of protein disulphide isomerase AGR2 confers tumorigenic properties
author_facet	Fessart, Delphine Domblides, Charlotte Avril, Tony Eriksson, Leif A Begueret, Hugues Pineau, Raphael Malrieux, Camille Dugot-Senant, Nathalie Lucchesi, Carlo Chevet, Eric Delom, Frederic
author_sort	Fessart, Delphine
title	Secretion of protein disulphide isomerase AGR2 confers tumorigenic properties
title_short	Secretion of protein disulphide isomerase AGR2 confers tumorigenic properties
title_full	Secretion of protein disulphide isomerase AGR2 confers tumorigenic properties
title_fullStr	Secretion of protein disulphide isomerase AGR2 confers tumorigenic properties
title_full_unstemmed	Secretion of protein disulphide isomerase AGR2 confers tumorigenic properties
title_sort	secretion of protein disulphide isomerase agr2 confers tumorigenic properties
description	The extracellular matrix (ECM) plays an instrumental role in determining the spatial orientation of epithelial polarity and the formation of lumens in glandular tissues during morphogenesis. Here, we show that the Endoplasmic Reticulum (ER)-resident protein anterior gradient-2 (AGR2), a soluble protein-disulfide isomerase involved in ER protein folding and quality control, is secreted and interacts with the ECM. Extracellular AGR2 (eAGR2) is a microenvironmental regulator of epithelial tissue architecture, which plays a role in the preneoplastic phenotype and contributes to epithelial tumorigenicity. Indeed, eAGR2, is secreted as a functionally active protein independently of its thioredoxin-like domain (CXXS) and of its ER-retention domain (KTEL), and is sufficient, by itself, to promote the acquisition of invasive and metastatic features. Therefore, we conclude that eAGR2 plays an extracellular role independent of its ER function and we elucidate this gain-of-function as a novel and unexpected critical ECM microenvironmental pro-oncogenic regulator of epithelial morphogenesis and tumorigenesis.
publisher	eLife Sciences Publications, Ltd
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4940162/
_version_	1613607149632487424

Secretion of protein disulphide isomerase AGR2 confers tumorigenic properties

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