ABSTRACT

Endometrial cancer is the most common gynecological cancer in the developed countries. Type II transmembrane serine proteases 4 (TMPRSS4) is a newly discovered transmembrane protein, which may be related to the invasion, metastasis of the tumor and the poor prognosis. This study aims to investigate the role of TMPRSS4 in endometrial cancer and the detailed molecular mechanism. The results showed that TMPRSS4 was highly expressed in human endometrial cancer cells (HEC1A and Ishikawa). TMPRSS4 knockdown inhibited proliferation of endometrial cancer cells. In TMPRSS4 knockdown cells, the invasion of cells was significantly supressed. The expression of E-cadherin was significantly enhanced, while the levels of fibronectin and vimentin decreased in TMPRSS4 knockdown cells, which indicated thatTMPRSS4 knockdown attenuated the EMT of cancer cells. TMPRSS4 positively regulated the activation of MAPK and AKT signaling pathways in endometrial cancer. In conclusion, this study indicated that TMPRSS4 may be associated with the progression of endometrial cancer through promoting proliferation, invasion and EMT via activation of MAPK and AKT in endometrial cancer cells. TMPRSS4 may be a new and more effective target or therapeutic strategy for treating endometrial cancer.

摘要

子宫内膜癌是发达国家最常见的妇科癌症。II型跨膜丝氨酸蛋白酶4（TMPRSS4）是一种新发现的跨膜蛋白，可能与肿瘤的侵袭、转移和预后不良有关。本研究旨在探讨TMPRSS4在子宫内膜癌中的作用及其详细的分子机制。结果表明，TMPRSS4在人子宫内膜癌细胞（HEC1A和Ishikawa）中高表达。TMPRSS4 敲低抑制子宫内膜癌细胞的增殖。在 TMPRSS4 敲低细胞中，细胞的侵袭被显着抑制。E-cadherin的表达显着增强，而TMPRSS4敲低的细胞中纤连蛋白和波形蛋白的水平降低，表明TMPRSS4敲低减弱了癌细胞的EMT。TMPRSS4在子宫内膜癌中正调控MAPK和AKT信号通路的激活。总之，本研究表明，TMPRSS4可能通过激活子宫内膜癌细胞中的MAPK和AKT促进增殖、侵袭和EMT与子宫内膜癌的进展有关。TMPRSS4 可能是治疗子宫内膜癌的一种新的、更有效的靶点或治疗策略。