在晚期宫颈癌治疗中，常因患者肿瘤细胞的转移而使疗效有限。肿瘤的侵袭和转移与癌细胞的黏附、迁移能力及细胞微丝的动态变化密切相关。微丝相关蛋白α-actinin4表达失控是肿瘤发生侵袭和转移的一个重要原因，目前有关α-actinin4在宫颈癌细胞内表达调控的分子机制尚不清晰。我们初步研究发现在宫颈癌HeLa细胞中NHERF1可调节细胞骨架并引起α-actinin4的表达下调。在此基础上，本课题拟采用多种方法确认NHERF1与α-actinin4在宫颈组织中的相互作用、探索该相互作用调节α-actinin4表达的分子机制，并研究该相互作用对宫颈癌细胞微丝骨架系统的组装和宫颈癌细胞转移的影响。本研究结果不仅有助于阐明在宫颈癌细胞中NHERF1调节α-actinin4表达和影响癌细胞转移的分子机制，而且可能揭示一种调节细胞微丝骨架变化的新机制，并为寻找新型宫颈癌治疗药物的作用靶标提供理论依据。

Cervical cancer is the second most common type of cancer for women worldwide. Much progress has been made in the prevention and control of cervical cancer in the early stages. However the treatment of advanced cervical cancers remains a significant challenge because of tumor invasion and metastasis. The invasive and metastatic potential of tumor cells are closely related with the adhesion and migration capabilities of tumor cells, which relies on the microfilament system. Actin-binding protein α-actinin 4 plays a critical role in regulating of microfilament system. Lines of evidence indicated that the abnormal expression of α-actinin 4 was essential to tumor invasion and metastasis; however, the molecular mechanism of α-actinin 4 expression regulation in cervical cancer cells was illusive. Our preliminary studies suggested that NHERF1 expression regulated cytoskeleton organization and retarded α-actinin 4 expression in cervical cancer cells. In this project, we will clarify the interaction of NHERF1 and α-actinin 4 via variety methods in cervical tissues, and also further study effects of this interaction on microfilament cytoskeleton system and metastasis in cervical cancer cells. The results of this study will help to elucidate the molecular mechanism of α-actinin 4 expression regulation and effects on cervical cancer metastasis. Moreover, it may reveal a novel mechanism for the regulation of cytoskeleton, and provide a theoretical basis of finding new targets for therapy in cervical cancer.