Water transport proteins-aquaporins (AQPs) in cancer biology

Abstract

As highly conserved ubiquitous proteins, aquaporins (AQPs) play an imperative role in the development and progression of cancer. By trafficking water and other small molecules, AQPs play a vital role in preserving the cellular environment. Due to their critical role in cell stability and integrity, it would make sense that AQPs are involved in cancer progression. When AQPs alter the cellular environment, there may be several downstream effects such as alterations in cellular osmolality, volume, ionic composition, and signaling pathways. Changes in the intracellular levels of certain molecules serving as second messengers are synchronized by AQPs. Thus AQPs regulate numerous downstream effector signaling molecules that promote cancer development and progression. In numerous cancer types, AQP expression has shown a correlation with tumor stage and prognosis. Furthermore, AQPs assist in angiogenic and oxidative stress related damaging processes critical for cancer progression. This indicates that AQP proteins may be a viable therapeutic target or biomarker of cancer prognosis.

Differential expression of epithelial sodium channels in human RCC associated with the prognosis and tumor stage: Evidence from integrate analysis

“…Besides the typical role of osmotic transepithelial and transcellular sodium regulators, AQPs are also involved in carcinogenesis 25 , 26 . They may facilitate angiogenesis, migration, tumor, and proliferation.…”

Insight into Salivary Gland Aquaporins

“…Each AQP type may participate in a specific carcinogenesis process ( Figure 4 ), including migration, invasion, metastasis, proliferation and drug resistance, which affect the prognosis of specific cancer type(s) [ 103 ]. AQPs play an essential role in at least three of the original hallmarks of cancer (angiogenic, invasion and metastasis) and in one of the cancer enabling-characteristics, as it contributes to and facilitates the transport of reactive oxygen species, which in turn increase tumor-promoting inflammation and induce genome instability and mutations [ 104 ].…”

Pathological role of ion channels and transporters in the development and progression of triple-negative breast cancer

“…In addition, deletion of “CCAAT”/enhancer binding protein (a family of transcription factors) β isoforms results in changes in mammary ductal morphogenesis and changes in expression of transport proteins such as AQP5, suggesting that AQP5 may be involved in mammary development [ 20 ]. Recent studies have shown that AQPs play carcinogenic roles by promoting angiogenesis, enhancing invasive and metastatic potential, and enhancing the transport of reactive oxygen species (ROS) [ 21 , 22 ]. In female-specific cancers, such as BC, AQP1, 3, and 5 are the most important AQPs, and they are been reported to be upregulated [ 23 ].…”