Ezrin-binding phosphoprotein 50 (EBP50)是一种必需的支架蛋白，用于上皮细胞极性。卵巢透明细胞癌（OCCC）细胞中膜型EBP50（Me-EBP50）的敲除（KO）引发了类上皮间质转化（EMT）的表型，伴随着细胞增殖的减少，迁移能力的加速以及癌症干细胞（CSC）样特性的诱导。EBP50与蛋白质共免疫沉淀的蛋白质的扫描质谱分析显示，Me-EBP50与肌球蛋白9（MYH9）相互作用强烈。用blebbistatin特异性抑制MYH9时，表现出与Me-EBP50敲除相同的表型，且blebbistatin处理增强了Me-EBP50敲除的效果。在临床样本中的OCCC细胞中，Me-EBP50和MYH9在顶部质膜共定位。具有Me-EBP50高和MYH9高分数组合的患者在总生存率和无进展生存率方面具有最佳预后。我们的数据表明，通过建立和维持上皮极性，Me-EBP50具有抑制肿瘤的作用。与之相反，Me-EBP50表达的丧失引发了EMT样表型，可能是由于MYH9功能障碍引起的；这导致细胞运动能力增强和CSC样特性增强，从而促进OCCC的进展。本文受版权保护，保留所有权利。

Ezrin-binding phosphoprotein 50 (EBP50) is a scaffold protein that is required for epithelial polarity. Knockout (KO) of membranous EBP50 (Me-EBP50) in ovarian clear cell carcinoma (OCCC) cells induced an epithelial-mesenchymal transition (EMT)-like phenotype, along with decreased proliferation, accelerated migration capability, and induction of cancer stem cell (CSC)-like properties. Shotgun proteomics analysis of proteins that co-immunoprecipitated with EBP50 revealed that Me-EBP50 strongly interacts with myosin 9 (MYH9). Specific inhibition of MYH9 with blebbistatin phenocopied Me-EBP50 knockout, and blebbistatin treatment potentiated the effects of Me-EBP50 knockout. In OCCC cells from clinical samples, Me-EBP50 and MYH9 were co-localized at the apical plasma membrane. Patients with a combination of Me-EBP50-high and MYH9-high scores had the best prognosis for overall and progression-free survival. Our data suggest that Me-EBP50 has tumor-suppressive effects through the establishment and maintenance of epithelial polarization. In contrast, loss of Me-EBP50 expression induces EMT-like phenotypes, probably due to MYH9 dysfunction; this results in increased cell mobility and enhanced CSC-like properties, which in turn promote OCCC progression.This article is protected by copyright. All rights reserved.