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 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.

NATURVETENSKAP Biologi Biokemi och molekylärbiologi hsv//swe
NATURAL SCIENCES Biological Sciences Biochemistry and Molecular Biology hsv//eng
EPITHELIAL-MESENCHYMAL TRANSITION
EXTRACELLULAR-MATRIX
ANTERIOR
GRADIENT-2
CELL-PROLIFERATION
PANCREATIC-CANCER
METASTASIS
LOCALIZATION
MIGRATION
SURVIVAL
TISSUE

Domblides, C. (författare)
Avril, T. (författare)
Eriksson, Leif A,1964Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology(Swepub:gu)xeleif (författare)
Begueret, H. (författare)
Pineau, R. (författare)
Malrieux, C. (författare)
Dugot-Senant, N. (författare)
Lucchesi, C. (författare)
Chevet, E. (författare)
Delom, F. (författare)
Göteborgs universitetInstitutionen för kemi och molekylärbiologi (creator_code:org_t)

Av författaren/redakt...: Fessart, D.; Domblides, C.; Avril, T.; Eriksson, Leif A ...; Begueret, H.; Pineau, R.; visa fler...; Malrieux, C.; Dugot-Senant, N.; Lucchesi, C.; Chevet, E.; Delom, F.; visa färre...

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