AMF/PGI通过MAPK-ERK信号通路介导子宫内膜癌的肿瘤发生。
AMF/PGI-mediated tumorigenesis through MAPK-ERK signaling in endometrial carcinoma.
作者信息
Li Yiran, Jia Yuanhui, Che Qi, Zhou Qian, Wang Kai, Wan Xiao-Ping
机构信息
Department of Obstetrics and Gynecology, Shanghai First People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China.
Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China.
出版信息
Oncotarget. 2015 Sep 22;6(28):26373-87. doi: 10.18632/oncotarget.4708.
Autocrine motility factor (AMF), which is also known as phosphoglucose isomerase (PGI), enhances tumor cell growth and motility. In this study, we found that AMF and its receptor were both highly expressed in Endometrial Carcinoma (EC) tissues compared to normal tissues. Levels of AMF were increased in serum of endometrial cancer patients. Downregulation of AMF by shRNA inhibited invasion, migration and proliferation as well as growth in a three-dimensional culture. AMF cytokine function, but not enzymatic activity of PGI, regulated tumorigenic activities of AMF. The MAPK-ERK1/2 pathway contributed to AMF-induced effects in EC cells. In agreement, Mek inhibitor decreased AMF-induced invasion, migration and proliferation of EC cells. In addition, in two mouse tumor metastasis models (EC cells delivered through left ventricle or intraperitoneally) AMF-silenced EC cells showed decreased tumor proliferative and metastatic capacities. We suggest that AMF/PGI is a potential therapeutic target in endometrial carcinoma.
自分泌运动因子（AMF），也被称为磷酸葡萄糖异构酶（PGI），可促进肿瘤细胞的生长和运动。在本研究中，我们发现与正常组织相比，AMF及其受体在子宫内膜癌（EC）组织中均高表达。子宫内膜癌患者血清中AMF水平升高。通过短发夹RNA（shRNA）下调AMF可抑制三维培养中的侵袭、迁移、增殖以及生长。AMF的细胞因子功能而非PGI的酶活性调节了AMF的致瘤活性。丝裂原活化蛋白激酶-细胞外信号调节激酶1/2（MAPK-ERK1/2）通路促成了AMF在EC细胞中的诱导作用。同样，Mek抑制剂可降低AMF诱导的EC细胞侵袭、迁移和增殖。此外，在两种小鼠肿瘤转移模型（通过左心室或腹腔注射递送EC细胞）中，AMF沉默的EC细胞显示出肿瘤增殖和转移能力下降。我们认为AMF/PGI是子宫内膜癌的一个潜在治疗靶点。
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