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 in vitro and in vivo 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 in vitro, and suppression of both tumor growth and lung metastasis in vivo. 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.