Aquaporins (AQPs) are a conserved family of transmembrane channel proteins that facilitate the selective transport of water, glycerol, and small solutes, thereby playing a pivotal role in maintaining cellular homeostasis. Beyond their classical role in fluid regulation, AQPs have emerged as key modulators of redox biology and cancer progression through their ability to transport hydrogen peroxide (H2O2), a central signaling molecule in oxidative stress. This redox-regulatory function, mediated predominantly by peroxiporins such as AQP3, AQP5, AQP8, and AQP9, influences diverse cellular outcomes including proliferation, apoptosis, migration, and stress adaptation. In cancer, dysregulated expression of AQPs has been linked to enhanced invasiveness, angiogenesis, and stemness, positioning them as critical drivers of tumor progression and potential therapeutic targets. Recent evidence highlights the clinical relevance of AQPs, with pharmacological inhibitors such as AqB013, Bacopasides, and small-molecule blockers under investigation for attenuating tumor growth and redox imbalance. Additionally, corticosteroid-mediated regulation of AQP3 and vasopressininduced trafficking of AQP2 illustrate the broader integration of AQPs within hormonal and inflammatory signaling pathways. By mediating water and reactive oxygen species flux across membranes, AQPs serve as gatekeepers of osmotic and oxidative balance at both the cellular and organ levels. This review synthesizes emerging insights into the mechanistic roles of AQPs in oxidative stress mitigation and tumor biology, while evaluating their translational potential as therapeutic targets. Understanding the dual role of AQPs in maintaining redox homeostasis and driving oncogenic signaling offers new opportunities for clinical intervention in cancer and oxidative stress-related pathologies.
Katta et al. (Mon,) studied this question.