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较高的自分泌运动因子/葡萄糖-6-磷酸异构酶表达与胃癌的肿瘤发生及较差预后相关。

Higher autocrine motility factor/glucose-6-phosphate isomerase expression is associated with tumorigenesis and poorer prognosis in gastric cancer.

作者信息

Ma Yu-Teng, Xing Xiao-Fang, Dong Bin, Cheng Xiao-Jing, Guo Ting, Du Hong, Wen Xian-Zi, Ji Jia-Fu

机构信息

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, China,

Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing, China,

出版信息

Cancer Manag Res. 2018 Oct 25;10:4969-4980. doi: 10.2147/CMAR.S177441. eCollection 2018.

DOI:10.2147/CMAR.S177441
PMID:30464597
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6208529/
Abstract

BACKGROUND

Glucose-6-phosphate isomerase (GPI) is a glycolytic-related enzyme that inter-converts 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 (<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.

摘要

背景

葡萄糖-6-磷酸异构酶（GPI）是一种与糖酵解相关的酶，在细胞质中催化葡萄糖-6-磷酸和果糖-6-磷酸相互转化。该蛋白也由癌细胞分泌到细胞外基质中，因此也被称为自分泌运动因子（AMF）。

方法

为阐明AMF/GPI在胃癌（GC）中的作用，我们收集了335例GC组织及相应的癌旁非癌组织，进行免疫组化研究，并分析AMF/GPI表达与患者临床病理特征之间的关系。

结果

发现GC组中AMF/GPI表达显著高于相应的非癌组织组（<0.001）。此外，AMF/GPI表达与患者较高的TNM分期和较差的预后呈正相关。通过Kaplan-Meier分析并根据Oncomine数据库，我们发现与正常黏膜相比，GC组织中AMF/GPI过表达，且AMF/GPI表达较高的患者预后较差。我们使用AMF/GPI沉默的GC细胞系来观察AMF/GPI的变化如何影响细胞表型。AMF/GPI敲低抑制了GC细胞的增殖、迁移、侵袭和糖酵解，并诱导其凋亡。

结论

这些发现表明，AMF/GPI过表达参与致癌过程并促进GC细胞的侵袭性表型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8599/6208529/b422d2823332/cmar-10-4969Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8599/6208529/7f79781d2cc8/cmar-10-4969Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8599/6208529/ac8ed7451ad9/cmar-10-4969Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8599/6208529/1324539d5c92/cmar-10-4969Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8599/6208529/1801fc18ec8c/cmar-10-4969Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8599/6208529/b422d2823332/cmar-10-4969Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8599/6208529/7f79781d2cc8/cmar-10-4969Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8599/6208529/ac8ed7451ad9/cmar-10-4969Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8599/6208529/1324539d5c92/cmar-10-4969Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8599/6208529/1801fc18ec8c/cmar-10-4969Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8599/6208529/b422d2823332/cmar-10-4969Fig5.jpg

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