Aquaporins (AQPs) are water channels that facilitate transport of water across cellular membranes. AQPs are overexpressed in several cancers. Especially in breast cancer, AQP5 overexpression correlates with spread to lymph nodes and poor prognosis. Previously, we showed that AQP5 expression reduced cell-cell adhesion by reducing levels of adherens and tight junction proteins (e.g., ZO1, plakoglobin and β-catenin) at the actual junctions. Here, we show that when targeted to the plasma membrane, the AQP5 C-terminal tail domain regulated junctional proteins. Moreover, that AQP5 interacted with ZO1, plakoglobin, β-catenin and desmoglein-2, which were all reduced at junctions upon AQP5 overexpression. Thus, our data suggest that AQP5 mediates the effect on cell-cell adhesion via interactions with junctional protein independently of AQP5 mediated water transport. AQP5 overexpression in cancers may thus contribute to carcinogenesis and cancer spread by two independent mechanisms: reduced cell-cell adhesion, a characteristic of epithelial-mesenchymal transition, and increased cell migration capacity via water transport.

中文翻译：

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Aquaporin-5对细胞粘附蛋白的调控：一个难以捉摸的“尾巴”故事

水通道蛋白（AQP）是水通道，可促进水跨细胞膜的运输。AQP在几种癌症中过表达。尤其是在乳腺癌中，AQP5过表达与扩散至淋巴结和预后不良有关。以前，我们表明AQP5表达通过降低实际连接处的粘附蛋白和紧密连接蛋白（例如ZO1，plakoglobin和β-catenin）的水平来降低细胞之间的粘附。在这里，我们显示当靶向质膜时，AQP5 C末端尾域调节连接蛋白。而且，AQP5与ZO1，plakoglobin，β-catenin和desmoglein-2相互作用，在AQP5过表达时，它们在连接处均减少。从而，我们的数据表明，AQP5通过与连接蛋白的相互作用独立于AQP5介导的水运输，介导了对细胞粘附的影响。因此，AQP5在癌症中的过度表达可能通过两种独立的机制促进癌变和癌症扩散：细胞间粘附减少，上皮-间质转化的特征以及通过水运输增加的细胞迁移能力。