Secretion of protein disulphide isomerase AGR2 confers tumorigenic properties.

Secretion of protein disulphide isomerase AGR2 confers tumorigenic properties.

Delphine Fessart , Charlotte Domblides, Tony Avril, Leif A Eriksson, Hugues Begueret, Raphael Pineau, Camille Malrieux, Nathalie Dugot-Senant, Carlo Lucchesi, Eric Chevet, Frederic Delom

Université de Bordeaux, France; University of Rennes 1, France; University of Gothenburg, Sweden; Hôpital Haut-Lévêque, France; Bergonié Cancer Institute, France

Elife. 2016 May 30;5. pii: e13887. doi: 10.7554/eLife.13887. [Epub ahead of print]
PMID:27240165 Free Article  Similar articles


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.

KEYWORDS: cancer biology; cell biology; human; mouse

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