Although a lack of functional PTEN contributes to tumorigenesis in a wide spectrum of human malignancies, little is known about the functional role of its overexpression in the tumors. The current study focused on PTEN overexpression in endometrial carcinoma (Em Ca). The functional impact of PTEN overexpression was assessed by Em Ca cell lines. Immunohistochemical analyses were also conducted using 38 Em Ca with morular lesions. Em Ca cell lines stably overexpressing PTEN (H6-PTEN) exhibited epithelial–mesenchymal transition (EMT)-like features, probably through β-catenin/Slug-meditated suppression of E-cadherin. PTEN overexpression also inhibited cell proliferation, accelerated cellular senescence, increased apoptotic features, and enhanced migration capability. Moreover, H6-PTEN cells exhibited cancer stem cell (CSC)-like properties, along with high expression of aldehyde dehydrogenase 1 and CD44s, a large ALDH 1high population, enriched spheroid formation, and β-catenin-mediated upregulation of cyclin D2, which is required for persistent CSC growth. In clinical samples, immunoreactivities for PTEN, as well as CSC-related molecules, were significantly higher in morular lesions as compared to the surrounding carcinomas. PTEN score was positively correlated with expression of nuclear β-catenin, cytoplasmic CD133, and CD44v6, and negatively with cell proliferation. Finally, estrogen receptor-α (ERα)-dependent expression of Ezrin-radixin-moesin-binding phophoprotein-50 (EBP50), a multifunctional scaffolding protein, acts as a negative regulator of morular formation by Em Ca cells through interacting with PTEN and β-catenin. In the abscess of ERα/EBP50 expression, PTEN overexpression and nuclear β-catenin stabilization promote the establishment and maintenance of morular phenotype associated with EMT/CSC-like features in Em Ca cells.

中文翻译：

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PTEN 过表达和核 β-连环蛋白稳定通过诱导子宫内膜癌中的上皮-间质转化和癌症干细胞样特性促进桑葚分化

尽管缺乏功能性 PTEN 会导致广泛的人类恶性肿瘤发生肿瘤，但对其过度表达在肿瘤中的功能作用知之甚少。目前的研究主要集中在子宫内膜癌 (Em Ca) 中的 PTEN 过表达。通过 Em Ca 细胞系评估 PTEN 过表达的功能影响。免疫组织化学分析也使用 38 Em Ca 与桑葚病变进行。稳定过表达 PTEN (H6-PTEN) 的 Em Ca 细胞系表现出类似上皮-间质转化 (EMT) 的特征，这可能是通过 β-catenin/Slug 介导的 E-钙粘蛋白抑制。PTEN 过表达还抑制细胞增殖，加速细胞衰老，增加凋亡特征，并增强迁移能力。此外，H6-PTEN 细胞表现出癌症干细胞 (CSC) 样特性，伴随着醛脱氢酶 1 和 CD44 的高表达、大量的 ALDH 1high 群体、富集的球体形成，以及 β-连环蛋白介导的细胞周期蛋白 D2 的上调，这是 CSC 持续生长所必需的。在临床样本中，与周围癌相比，桑葚病变中 PTEN 以及 CSC 相关分子的免疫反应性明显更高。PTEN 评分与核 β-连环蛋白、细胞质 CD133 和 CD44v6 的表达呈正相关，与细胞增殖呈负相关。最后，Ezrin-radixin-moesin-binding phophoprotein-50 (EBP50) 的雌激素受体-α (ERα) 依赖性表达，一种多功能支架蛋白，通过与 PTEN 和 β 相互作用，作为 Em Ca 细胞的桑葚形成的负调节因子-连环蛋白。在ERα/EBP50表达的脓肿中，