AGR2: The Covert Driver and New Dawn of Hepatobiliary and Pancreatic Cancer Treatment

Abstract

The anterior gradient protein 2 (AGR2) plays a crucial role in facilitating the formation of protein disulfide bonds within the endoplasmic reticulum (ER). Research suggests that AGR2 can function as an oncogene, with its heightened expression linked to the advancement of hepatobiliary and pancreatic cancers through invasion and metastasis. Notably, AGR2 not only serves as a pro-oncogenic agent but also as a downstream targeting protein, indirectly fostering cancer progression. This comprehensive review delves into the established functions and expression patterns of AGR2, emphasizing its pivotal role in cancer progression, particularly in hepatobiliary and pancreatic malignancies. Furthermore, AGR2 emerges as a potential cancer prognostic marker and a promising target for immunotherapy, offering novel avenues for the treatment of hepatobiliary and pancreatic cancers and enhancing patient outcomes.

Keywords: AGR2; cancer invasion and prognosis; endoplasmic reticulum stress (ERS); hepatobiliary and pancreatic cancer; immunotherapy.

Figure 1

Endoplasmic reticulum stress and multiple proteins regulate AGR2 expression.

Figure 2

Endoplasmic reticulum stress promotes AGR2 overexpression, which, on the one hand, is involved in the progression and deterioration of liver disease by causing an increase in lipids; on the other hand, AGR2 overexpression induces immune cell death and promotes hepatobiliary and pancreatic Cancer invasion.