Anterior gradient 2 is involved in the post-transcriptional regulation of β-dystroglycan

Abstract

Anterior gradient 2 (AGR2) is a protein disulfide isomerase over-expressed in numerous types of cancer. Although AGR2 plays a role in ER homeostasis, its function(s) in tumorigenesis is still elusive. Here we demonstrate that AGR2 is involved in the regulation of the β-subunit of dystroglycan (β-DG), a component of the multi-protein complex linking the extracellular matrix and cytoskeletal network. In breast cancer cells, AGR2 over-expression led to the up-regulation of β-DG but not that of α-DG, while the transcript levels of these subunits were unchanged. Conversely, the reduced expression of AGR2 caused the down-regulation of β-DG. Interestingly, induced expression of AGR2 increased the degree of co-localization of AGR2 and β-DG in the cytoplasm suggesting that AGR2 facilitates the trafficking of β-DG. In addition, AGR2 over-expression caused the re-arrangement of the actin cytoskeletal network. Presumably over-expressed AGR2 up-regulates β-DG post-transcriptionally and facilitates its trafficking, which then causes re-arrangement of the cytoskeletal network, which plays a role in the adhesion and invasion of cancer cells.