雌激素在子宫腺肌症的发病过程中起到了重要作用，研究其作用机制对腺肌症的治疗有重要意义。极性蛋白表达量或胞内定位异常介导的细胞极性破坏参与上皮肿瘤的发生，然而其在腺肌症发生中的作用尚且不明。我们研究发现：雌激素不仅能促使极性蛋白Scribble泛素化降解，而且能改变其胞内定位，从而破坏内膜腺上皮细胞极性；腺上皮细胞中Scribble胞内定位受棕榈酰化修饰调节，而雌激素能下调Scribble棕榈酰化修饰水平。据此我们提出假说：雌激素通过下调Scribble棕榈酰化修饰促进其胞浆转位参与子宫腺肌症的发生。本研究拟从动物、细胞、临床三个水平，利用腺肌症小鼠模型、人原代内膜腺上皮细胞及临床组织标本，以三维培养、免疫组化、免疫共沉淀等方法，探讨雌激素介导的Scribble胞浆转位在子宫腺肌症发生中的作用及其分子机制。本研究将从细胞极性这个新视角为揭示子宫腺肌症的发病机制、为子宫腺肌症的防治提供新思路。

Estrogen plays an important role in the pathogenesis of adenomyosis and studying its mechanism is of great significance for the treatment of adenomyosis. Destruction of cell polarity mediated by abnormal expression or mislocalization of polarity protein is involved in the process of epithelial tumor, however, its role in the occurrence of adenomyosis is unknown. Our research found that estrogen can not only promote the degradation of the polarity protein Scribble by ubiquitinated proteasome pathway, but also change its intracellular localization, thereby destroying the polarity of glandular epithelial cells; the intracellular localization of Scribble in glandular epithelial cells is dynamically regulated by S-palmitoylation and estrogen can reduce the level of palmitoylated Scribble. Based on the results of the previous research, we propose a hypothesis that estrogen promotes Scribble cytoplasmic translocation by regulating its palmitoylation in diffuse adenomyosis. This study intends to use animal model of adenomyosis, human primary endometrial epithelial cells and clinical tissue specimens from animal, cell, and clinical levels to explore the role and molecular mechanism of estrogen-mediated Scribble cytoplasmic translocation in the development of diffuse adenomyosis by methods of three-dimensional culture, immunohistochemistry and protein immunoprecipitation. This research will provide new ideas for revealing the pathogenesis of adenomyosis and molecular targets for the development of new drugs for the treatment of adenomyosis from the new perspective of cell polarity.