Epithelial cell polarity defects support cancer progression. It is thus crucial to decipher the functional interactions within the polarity protein network. Here we show that Drosophila Girdin and its human ortholog (GIRDIN) sustain the function of crucial lateral polarity proteins by inhibiting the apical kinase aPKC. Loss of GIRDIN expression is also associated with overgrowth of disorganized cell cysts. Moreover, we observed cell dissemination from GIRDIN knockdown cysts and tumorspheres, thereby showing that GIRDIN supports the cohesion of multicellular epithelial structures. Consistent with these observations, alteration of GIRDIN expression is associated with poor overall survival in subtypes of breast and lung cancers. Overall, we discovered a core mechanism contributing to epithelial cell polarization from flies to humans. Our data also indicate that GIRDIN has the potential to impair the progression of epithelial cancers by preserving cell polarity and restricting cell dissemination.

上皮细胞极性缺陷支持癌症进展。因此，至关重要的是解密极性蛋白质网络内的功能相互作用。在这里，我们显示果蝇Girdin及其人类直系同源物（GIRDIN）通过抑制顶端激酶aPKC来维持至关重要的侧向极性蛋白的功能。GIRDIN表达的丧失也与无组织细胞囊肿的过度生长有关。此外，我们观察到细胞从GIRDIN击倒的囊肿和肿瘤球的扩散，从而表明GIRDIN支持多细胞上皮结构的凝聚。与这些观察结果一致，对吉尔丁进行了修改表达与乳腺癌和肺癌亚型的总体生存不良有关。总体而言，我们发现了导致果蝇从人到人的上皮细胞极化的核心机制。我们的数据还表明，GIRDIN有潜力通过保留细胞极性和限制细胞扩散来损害上皮癌的进展。