The role of AGR2 and AGR3 in cancer: similar but not identical.

In the past decades, highly related members of the protein disulphide isomerase family, anterior gradient protein AGR2 and AGR3, attracted researchers' attention due to their putative involvement in developmental processes and carcinogenesis. While AGR2 has been widely demonstrated as a metastasis-related protein whose elevated expression predicts worse patient outcome, little is known about AGR3's role in tumour biology. Thus, we aim to confront the issue of AGR3 function in physiology and pathology in the following review by comparing this protein with the better-described homologue AGR2. Relying on available data and in silico analyses, we show that AGR proteins are co-expressed or uncoupled in context-dependent manners in diverse carcinomas and healthy tissues. Further, we discuss plausible roles of both proteins in tumour-associated processes such as differentiation, proliferation, migration, invasion and metastasis. This work brings new hints and stimulates further thoughts on hitherto unresolved conundrum of anterior gradient protein function.