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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2016-05-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/13887 |
| _version_ | 1811199744783941632 |
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| author | Delphine Fessart Charlotte Domblides Tony Avril Leif A Eriksson Hugues Begueret Raphael Pineau Camille Malrieux Nathalie Dugot-Senant Carlo Lucchesi Eric Chevet Frederic Delom |
| author_facet | Delphine Fessart Charlotte Domblides Tony Avril Leif A Eriksson Hugues Begueret Raphael Pineau Camille Malrieux Nathalie Dugot-Senant Carlo Lucchesi Eric Chevet Frederic Delom |
| author_sort | Delphine Fessart |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T01:53:34Z |
| format | Article |
| id | doaj.art-3876518ea92442c383684c20fc26b282 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T01:53:34Z |
| publishDate | 2016-05-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-3876518ea92442c383684c20fc26b2822022-12-22T03:52:52ZengeLife Sciences Publications LtdeLife2050-084X2016-05-01510.7554/eLife.13887Secretion of protein disulphide isomerase AGR2 confers tumorigenic propertiesDelphine Fessart0https://orcid.org/0000-0001-7566-5670Charlotte Domblides1Tony Avril2Leif A Eriksson3Hugues Begueret4Raphael Pineau5Camille Malrieux6Nathalie Dugot-Senant7Carlo Lucchesi8Eric Chevet9https://orcid.org/0000-0001-5855-4522Frederic Delom10https://orcid.org/0000-0002-4600-7633Oncogenesis, Stress and Signaling Laboratory, ERL440 Inserm, Université de Rennes 1, Rennes, France; Centre de Lutte Contre le Cancer Eugène Marquis, Rennes, France; INSERM U1218, Actions for onCogenesis understanding and Target Identification in ONcology (ACTION), Bordeaux, France; Bergonié Cancer Institute, Bordeaux, FranceUniversité de Bordeaux, Bordeaux, FranceOncogenesis, Stress and Signaling Laboratory, ERL440 Inserm, Université de Rennes 1, Rennes, France; Centre de Lutte Contre le Cancer Eugène Marquis, Rennes, FranceDepartment of Chemistry and Molecular Biology, University of Gothenburg, Göteborg, SwedenHôpital Haut-Lévêque, Bordeaux, FranceAnimalerie mutualisée, Université de Bordeaux, Bordeaux, FranceINSERM U1218, Actions for onCogenesis understanding and Target Identification in ONcology (ACTION), Bordeaux, France; Bergonié Cancer Institute, Bordeaux, France; Université de Bordeaux, Bordeaux, FranceUniversité de Bordeaux, Bordeaux, FranceBergonié Cancer Institute, Bordeaux, France; Site de Recherche Intégrée sur le Cancer, Bordeaux Recherche Intégrée en Oncologie, Bordeaux, FranceOncogenesis, Stress and Signaling Laboratory, ERL440 Inserm, Université de Rennes 1, Rennes, France; Centre de Lutte Contre le Cancer Eugène Marquis, Rennes, FranceINSERM U1218, Actions for onCogenesis understanding and Target Identification in ONcology (ACTION), Bordeaux, France; Bergonié Cancer Institute, Bordeaux, France; Université de Bordeaux, Bordeaux, FranceThe 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.https://elifesciences.org/articles/13887AGR2cancerorganoidsprotein disulphide isomeraseendoplasmic reticulum |
| spellingShingle | Delphine Fessart Charlotte Domblides Tony Avril Leif A Eriksson Hugues Begueret Raphael Pineau Camille Malrieux Nathalie Dugot-Senant Carlo Lucchesi Eric Chevet Frederic Delom Secretion of protein disulphide isomerase AGR2 confers tumorigenic properties eLife AGR2 cancer organoids protein disulphide isomerase endoplasmic reticulum |
| title | 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_short | Secretion of protein disulphide isomerase AGR2 confers tumorigenic properties |
| title_sort | secretion of protein disulphide isomerase agr2 confers tumorigenic properties |
| topic | AGR2 cancer organoids protein disulphide isomerase endoplasmic reticulum |
| url | https://elifesciences.org/articles/13887 |
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