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.
Highlights
Endometrial carcinoma (EC) is the most frequent gynecological malignancy and a leading cause of cancer death in women worldwide
We found that Autocrine motility factor (AMF) and its receptor were both highly expressed in Endometrial Carcinoma (EC) tissues compared to normal tissues
AMF and its receptor AMFR expressions were evaluated in normal endometrium (32 samples) and endometrial cancer (72 samples) tissues using immuno histochemistry (IHC)
Summary
Endometrial carcinoma (EC) is the most frequent gynecological malignancy and a leading cause of cancer death in women worldwide. Cancer progression and metastasis are controlled by various extracellular growth factors and cytokines [5, 6] One such factor, autocrine motility factor (AMF), which is known as phosphoglucose isomerase (PGI), was originally isolated from the conditioned medium of melanoma cancer cells and stimulates both direct and random cell migration [7, 8]. Autocrine motility factor (AMF), which is known as phosphoglucose isomerase (PGI), was originally isolated from the conditioned medium of melanoma cancer cells and stimulates both direct and random cell migration [7, 8] This protein behaves as a housekeeping cytosolic enzyme of sugar metabolism and plays a key role in both glycolysis and gluconeogenesis pathways, catalyzing the interconversion of glucose 6-phosphate and fructose 6-phosphate [9]. Several researchers independently found that secreted AMF, a tumor-secreted cytokine, is involved in regulation oncogenesis and tumor progression in various human cancers including breast [14, 15], lung [16], liver [17, 18], melanoma [19]and osteogenic sarcoma [20]
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