癌症中的细胞变化包括细胞增殖、细胞迁移、细胞间粘附和细胞极性的改变。体外研究表明，水通道、水通道蛋白-1 (AQP1) 和 AQP3 可以影响细胞迁移和细胞间粘附。值得注意的是，我们之前表明，AQP1 过度表达会降低细胞间粘附蛋白的水平，而 AQP3 在正常上皮细胞中过度表达时会增加水平。 AQP1和AQP3在乳腺癌中的表达与乳腺癌患者的淋巴结转移、复发和不良生存相关。在本研究中，我们通过研究主要极性蛋白 Scribble 与 AQP1 和 AQP3 之间的关系，研究 AQP1 和 AQP3 是否影响乳腺癌细胞极性。在乳腺癌组织样本中，AQP1、AQP3和Scribble的蛋白表达量并未表现出明显的相关性。然而，在 GST 下拉测定中，AQP1 和 AQP3 与 Scribble 相互作用。 AQP1 过表达减少了 3D 球体的大小，并降低了细胞与细胞接触处的 Scribble 水平，而 AQP3 过表达显示与对照相比，球体大小没有显着变化，AQP3 过表达还降低了细胞与细胞接触处的 Scribble 水平。值得注意的是，AQP1 过表达会增加细胞迁移，并诱导细胞从迁移的乳腺癌细胞片中脱离和扩散，而 AQP3 过表达则不会。因此，AQP1 和 AQP3 对 3D 生长的乳腺癌球体有不同的影响，尤其是 AQP1 可能通过对细胞连接和细胞极性蛋白产生负面影响以及增加细胞迁移和细胞脱离来促进癌症的发展和扩散。

Cellular changes in carcinomas include alterations in cell proliferation, cell migration, cell-cell adhesion and cellular polarity. In vitro studies have revealed that the water channels, aquaporin-1 (AQP1) and AQP3 can influence cell migration and cell-cell adhesion. Of note, we previously showed that AQP1 overexpression reduced levels of cell-cell adhesion proteins, whereas AQP3 increased levels when overexpressed in normal epithelial cells. Expression of AQP1 and AQP3 in breast carcinoma is associated with lymph node metastasis, recurrence, and poor survival of breast cancer patients. In this study, we investigated if AQP1 and AQP3 affected cell polarity in breast cancer by studying the relationship between the major polarity protein Scribble and AQP1 and AQP3. In breast cancer tissue samples, the protein expression of AQP1, AQP3 and Scribble did not show an obvious correlation. However, in a GST pull-down assay, AQP1 and AQP3 interacted with Scribble. AQP1 overexpression reduced the size of 3D spheroids as well as reduced Scribble levels at cell-cell contacts, whereas AQP3 overexpression showed no significant change in spheroid size compared to control, AQP3 overexpression also reduced Scribble levels at cell-cell contacts. Of note, AQP1 overexpression increased cell migration and induced cell detachment and dissemination from migrating breast cancer cell sheets, whereas AQP3 overexpression did not. Thus, AQP1 and AQP3 differentially affect 3D grown breast cancer spheroids and especially AQP1 may contribute to cancer development and spread via negatively affecting cellular junctions and cell polarity proteins as well as increasing cell migration and cell detachment.