Anterior gradient protein 2 promotes survival, migration and invasion of papillary thyroid carcinoma cells

Gennaro Di Maro, Paolo Salerno, Kristian Unger, Francesca M. Orlandella, Mario Monaco, Gennaro Chiappetta, Gerry Thomas, Malgorzata Oczko-Wojciechowska, Mariorosario Masullo, Barbara Jarzab, Massimo Santoro, Giuliana Salvatore

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Through a transcriptome microarray analysis, we have isolated Anterior gradient protein 2 (AGR2) as a gene up-regulated in papillary thyroid carcinoma (PTC). AGR2 is a disulfide isomerase over-expressed in several human carcinomas and recently linked to endoplasmic reticulum (ER) stress. Here, we analyzed the expression of AGR2 in PTC and its functional role.Methods: Expression of AGR2 was studied by immunohistochemistry and real time PCR in normal thyroids and in PTC samples. The function of AGR2 was studied by knockdown in PTC cells and by ectopic expression in non-transformed thyroid cells. The role of AGR2 in the ER stress was analyzed upon treatment of cells, expressing or not AGR2, with Bortezomib and analyzing by Western blot the expression levels of GADD153.Results: PTC over-expressed AGR2 at mRNA and protein levels. Knockdown of AGR2 in PTC cells induced apoptosis and decreased migration and invasion. Ectopic expression of AGR2 in non-transformed human thyroid cells increased migration and invasion and protected cells from ER stress induced by Bortezomib.Conclusions: AGR2 is a novel marker of PTC and plays a role in thyroid cancer cell survival, migration, invasion and protection from ER stress.

Original languageEnglish
Article number160
JournalMolecular Cancer
Volume13
Issue number1
DOIs
Publication statusPublished - Jun 30 2014

Keywords

  • AGR2
  • Endoplasmic reticulum stress
  • Migration and invasion
  • Survival
  • Thyroid cancer

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Oncology

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