Zhu Lin-Yan, Zhang Wen-Ming, Yang Xiao-Mei, Cui Lining, Li Jun, Zhang Yan-Li, Wang Ya-Hui, Ao Jun-Ping, Ma Ming-Ze, Lu Huan, Ren Yuan, Xu Shao-Hua, Yang Guang-Dong, Song Wei-Wei, Wang Jing-Hao, Zhang Xiao-Dan, Zhang Rong, Zhang Zhi-Gang
Department of Obstetrics and Gynecology, Fengxian Hospital, Southern Medical University, Shanghai 201499, China; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200240, China; Department of Obstetrics and Gynecology, Ningbo First Hospital, Ninbo, Zhejiang 3015000, China.
Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Cancer Lett. 2015 Jul 10;363(1):71-82. doi: 10.1016/j.canlet.2015.04.002. Epub 2015 Apr 9.
Ovarian cancer remains the disease with the highest associated mortality rate of gynecologic malignancy due to cancer metastasis. Rearrangement of actin cytoskeleton by cytoskeleton protein plays a critical role in tumor cell metastasis. MICAL-L2, a member of MICAL family, can interact with actin-binding proteins, regulate actin cross-linking and coordinate the assembly of adherens junctions and tight junctions. However, the roles of MICAL-L2 in tumors and diseases have not been explored. In this study, we found that MICAL-L2 protein is significantly up-regulated in ovarian cancer tissues along with FIGO stage and associated with histologic subgroups of ovarian cancer. Silencing of MICAL-L2 suppressed ovarian cancer cell proliferation, migration and invasion ability. Moreover, silencing of MICAL-L2 prevented nuclear translocation of β-catenin, inhibited canonical wnt/β-catenin signaling and induced the mesenchymal-epithelial transition (MET). Taken together, our data indicated that MICAL-L2 may be an important regulator of epithelial-mesenchymal transition (EMT) in ovarian cancer cells and a new therapeutic target for interventions against ovarian cancer invasion and metastasis.
由于癌症转移，卵巢癌仍然是妇科恶性肿瘤中死亡率最高的疾病。细胞骨架蛋白对肌动蛋白细胞骨架的重排在肿瘤细胞转移中起关键作用。MICAL-L2是MICAL家族的一员，可与肌动蛋白结合蛋白相互作用，调节肌动蛋白交联，并协调黏附连接和紧密连接的组装。然而，MICAL-L2在肿瘤和疾病中的作用尚未得到探索。在本研究中，我们发现MICAL-L2蛋白在卵巢癌组织中随着国际妇产科联盟（FIGO）分期显著上调，并与卵巢癌的组织学亚组相关。沉默MICAL-L2可抑制卵巢癌细胞的增殖、迁移和侵袭能力。此外，沉默MICAL-L2可阻止β-连环蛋白的核转位，抑制经典的Wnt/β-连环蛋白信号通路，并诱导间充质-上皮转化（MET）。综上所述，我们的数据表明，MICAL-L2可能是卵巢癌细胞上皮-间质转化（EMT）的重要调节因子，也是干预卵巢癌侵袭和转移的新治疗靶点。
