Sema4C通过AKT通路决定宫颈癌进展及其机制研究.doc

  Sema4C determines aggressiveness of human cervical cancers by the AKT pathway# WU Mingfu, YANG Jie, LI Nin, LIU Lijiang** 5 10 15 20 25 30 (Department of Obstetrics and Gynecology, Tongji Medical College, Huazhong University of Science and Technology, WuHan 430030) Abstract: Increasing evidences indicated that Semaphorins involved in tumorigenesis and tumor development. In our previous observations, a trans-membrane protein Sema4C has been identified as a novel molecular target in human breast cancer and Sema4C abnormal expression in the lymphatic endothelial cells of human cervical cancers provided another new molecular machenism for lymphatic metastasis of cervical cancer. However, the role and function of Sema4C in human cervical cancers are stiil unkown. In this study, we first detected the relationship between Sema4C expression and malignant behaviors in four different human cervical cancer cells, and then further investigated the effect of specific silencing Sema4C on malignant phenotype and its molecular mechanism in different tumor cell lines was. We observed the universal high expression of Sema4C in cervical cancer cell lines, but Sema4C expression was the strongest in Caski cells. Sema4C siRNA significantly inhibited the capabilities of invasion and proliferation of Caski cells. Furthermore, decreased phosphorylation levels of AKTThr-308 but no obvious alteration of the expression of total AKT and phosphorylation of AKTSer-473 were showed after effective silencing of Sema4C. These findings above showed that Sema4C promotes malignant behaviors of cervical cancer cells via altered phosphorylation levels of AKTThr-308, suggesting that Sema4C may be a novel therapeutic target for the treatment of cervical cancer. Keywords: Cervical cancer; Sema4C; AKT Introduction Cervical cancer is the second malignancies in the world. The lymphatic metastasis often occurs in the earlier clinical stage, such as CIN Ⅲ. The status of Lymphatic endothelial cells (named as