AMF/PGI-mediated tumorigenesis through MAPK-ERK signaling in endometrial carcinoma

// Yiran Li 1 , Yuanhui Jia 2 , Qi Che 2 , Qian Zhou 2 , Kai Wang 2 , Xiao-Ping Wan 3 1 Department of Obstetrics and Gynecology, Shanghai First People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China 2 Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China 3 Department of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China Correspondence to: Kai Wang, e-mail: kaiwangcn@yahoo.com Xiao-Ping Wan, e-mail: wanxiaoping62@126.com Keywords: endometrial carcinoma, Autocrine Motility Factor (AMF)/PhosphoGlucose Isomerase (PGI), MAPK signaling pathway, invasion, prognosis Received: April 29, 2015 Accepted: July 08, 2015 Published: July 20, 2015 ABSTRACT 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.