AQP7 suppresses cell stemness and metastasis by targeting Wnt signaling in basal-like breast cancer.

[BACKGROUND] Breast cancer is a leading cause of cancer-related death among women worldwide. Aquaporin 7 (AQP7), a transmembrane protein facilitating the transport of glycerol, and/or water across plasma membranes, has been found the aberrant expression and dysfunction in various types of human cancer.

[RESEARCH DESIGN AND METHODS] In this study, we revealed an aberrant downregulation of AQP7 in basal-like breast cancer. We performed functional assays and using basal-like human breast cancer cells with or without expression of AQP7, including cancer cell stemness, cell migration and invasion, and tumorigenesis in mice.

[RESULTS] Overexpression of AQP7 showed a significant inhibition of cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and cancer cell stemness , and suppression of both tumor growth and lung metastasis . Consistencely, knockdown of AQP7 induced cancer cell stemness and migration and invasion. Pathway analysis of the AQP7-regulated genes indicated significant enrichment in pathways regulating the cell cycle and Wnt-β-catenin signaling, which were further experimentally validated.

[CONCLUSIONS] The current study demonstrates a tumor-suppressive function of AQP7 in breast cancer through inhibiting the cell cycle, EMT, and cancer cell stemness. AQP7 holds potential as a therapeutic target to treat breast cancer.