The role of aquaporin-5 in cancer cell migration: A potential active participant

Overexpression of aquaporin-5 has been observed in the cancers of breast, lung, colon, esophagus, liver, ovaries, cervix, and in leukemia. The high levels of aquaporin-5 may contribute to cancer progression and metastasis to lymph nodes. Activation of the migration machinery underlies metastasis, and this may be promoted by aquaporin-5 via increased water influx to the leading edge, changes in cytoskeletal stability and prospectively Rho GTPase signaling. Aquaporin-5 also activates Ras, increasing proliferation and potentially also contributing to increased cell movement. [Display omitted] •AQP5 is upregulated in a number of cancer types, where it is associated with increased tendencies to metastasize and poor prognosis.•Cell culture assays indicate that AQP5 may regulate cell migration and thus metastasis.•AQP5 may increase cell migration by allowing water influx causing slight swelling and space for actin polymerization in the leading edge.•Phosphorylation of AQP5 may activate downstream signaling effectors to stimulate proliferation and migration. Emerging data identifies the water channel aquaporin-5 as a major player in multiple cancers. Over-expression of aquaporin-5 has been associated with increased metastasis and poor prognosis, suggesting that aquaporin-5 may enhance cancer cell migration. This review aims to highlight the current knowledge and hypothesis regarding downstream signaling partners of aquaporin-5 in relation to cancer cell migration. The molecular mechanisms that link aquaporin-5 to cell migration are not completely understood. Aquaporin-5 may promote cell movement by increasing water uptake into the front of the cell allowing local swelling. Aquaporin-5 may also activate extracellular-regulated kinases, increasing proliferation and potentially stimulating the migration machinery. Thus, further studies are warranted to identify the underlying mechanisms and signaling pathways. This will reveal whether aquaporin-5 and downstream effectors could be targets for developing new cancer therapeutics.