AQP8 inhibits colorectal cancer growth and metastasis by down-regulating PI3K/AKT signaling and PCDH7 expression.

Abstract

Colorectal cancer (CRC) is one of the most common malignant cancers and the leading cause of cancer-related deaths in worldwide. Although the monoclonal antibody therapy is prescribed for CRC, the metastasis resistant to therapy is the major cause of death of patients with CRC, which indicating the urgent demands for new therapeutic targets discovery. Aquaporin 8 (AQP8) has been identified alter expressed in several cancers including breast cancer, lung cancer and prostatic carcinoma. Our study demonstrated the functional significance of AQP8 in CRC cells growth and metastasis. Over-expression of AQP8 remarkably decreased growth, aggressiveness and colony formation in the CRC SW480 and HT-29 cells. Mechanistically, AQP8 over-expression inhibited tumorigenic phenotype by inactivating PI3K/AKT signaling and inhibiting PCDH7 expression. Furthermore, in vivo studies using nude mice xenograft and metastasis model identified the pivotal role of AQP8 in CRC cells growth and metastasis. Taken together, the present study verifies the vital role of the endogenous AQP8 in colorectal cancer progression.