The Expanding Role of Aquaporin-1, Aquaporin-3 and Aquaporin-5 as Transceptors: Involvement in Cancer Development and Potential Druggability

Aquaporins (AQPs) are transmembrane proteins that facilitate the transport of water and small solutes, including glycerol, hydrogen peroxide and ions, across cell membranes. Beyond their established physiological roles in water regulation and metabolic processes, AQPs also exhibit receptor-like signaling activities in cancer-associated signaling pathways, integrating the dual roles of transporters and receptors, hence functioning as transceptors. This dual functionality underpins their critical involvement in cancer biology, where AQPs play key roles in promoting cell proliferation, migration, and invasion, contributing significantly to carcinogenesis. Among the AQPs, AQP1, AQP3 and AQP5 have been consistently identified as being aberrantly expressed in various tumor types. Their overexpression is strongly associated with tumor progression, metastasis, and poor patient prognosis. This review explores the pivotal roles of AQP1, AQP3 and AQP5 as transceptors in cancer biology, underscoring their importance as pharmacological targets. It highlights the urgent need for the development of effective modulators to target these AQPs, offering a promising avenue to enhance current therapeutic approaches for cancer treatment.