ARG1 functions as a tumor suppressor in breast cancer.

Arginase I (ARG1) is a cytosolic enzyme that catalyzes the hydrolysis of L-arginine to L-ornithine and urea. The association of ARG1 with cancer has mostly been focused on the ARG1 released by tumor-associated myeloid cells in tumor microenvironment. However, the role of ARG1 expressed in cancer cells is unclear. Here, we showed that the expression of ARG1 in human breast cancer (BC) is related to a good prognosis in BC patients. Overexpression of ARG1 suppresses BC cell proliferation and migration in vitro and xenograft tumor growth and development in mouse models. Furthermore, ARG1 expression down-regulates the expression of p-AKT, leading to the de-activation of AKT signal pathway in BC cells. Thus, our results established that in contrast to the role of ARG1 released from tumor-associated myeloid cells in tumor microenvironment that promotes tumor immune escape, ARG1 expressed in BC cells suppresses AKT signaling pathway and functions as a tumor suppressor.