Higher autocrine motility factor/glucose-6-phosphate isomerase expression is associated with tumorigenesis and poorer prognosis in gastric cancer
Received 16 June 2018
Accepted for publication 6 August 2018
Published 25 October 2018 Volume 2018:10 Pages 4969—4980
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Colin Mak
Peer reviewer comments 3
Editor who approved publication: Dr Antonella D'Anneo
Yu-Teng Ma,1,2 Xiao-Fang Xing,1 Bin Dong,3 Xiao-Jing Cheng,1 Ting Guo,1 Hong Du,1 Xian-Zi Wen,1 Jia-Fu Ji1,2
1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, China; 2Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing, China; 3Department of Pathology, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China
Background: Glucose-6-phosphate isomerase (GPI) is a glycolytic-related enzyme that interconverts glucose-6-phosphate and fructose-6-phosphate in the cytoplasm. This protein is also secreted into the extracellular matrix by cancer cells and is, therefore, also called autocrine motility factor (AMF).
Methods: To clarify the roles of AMF/GPI in gastric cancer (GC), we collected 335 GC tissues and the corresponding adjacent noncancerous tissues, performed immunohistochemical studies, and analyzed the relationship between AMF/GPI expression and the patients’ clinicopathologic features.
Results: AMF/GPI expression was found to be significantly higher in the GC group than in the corresponding noncancerous tissue group (P<0.001). Additionally, AMF/GPI expression positively associated with a higher TNM stage and poorer prognosis in patients. Through Kaplan–Meier analysis and according to the Oncomine database, we found that AMF/GPI was overexpressed in GC tissues compared to normal mucosa, and the patients with higher AMF/GPI expression had poorer outcomes. We used AMF/GPI-silenced GC cell lines to observe how changes in AMP/GPI affect cellular phenotypes. AMF/GPI knockdown suppressed proliferation, migration, invasion, and glycolysis, and induced apoptosis in GC cells.
Conclusion: These findings suggest that AMF/GPI overexpression is involved in carcinogenesis and promotes the aggressive phenotypes of GC cells.
Keywords: gastric cancer, glucose-6-phosphate isomerase, autocrine motility factor, tumorigenesis, prognosis, metabolism
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