Interleukin-23 promotes the migration and invasion of gastric cancer cells by inducing epithelial-to-mesenchymal transition via the STAT3 pathway

Abstract Gastric cancer is an important health problem, being the fifth most common cancer and the third leading cause of cancer-related death worldwide. Aberrant protein translation contributes to the oncogenesis and development of cancers, and upregulation of translation initiation factor eIF4A1 has been observed in several kinds of malignancies. However, the role of eIF4A1 in gastric cancer progression remains unclear. In this study, we found that the expression of eIF4A1, a component of translation initiation complex, was increased in gastric cancer. High expression of eIF4A1 was positively associated with poor tumor differentiation, late T stage, lymph node metastasis, advanced TNM stage, and poor prognosis in patients with gastric cancer. Overexpression of eIF4A1 promoted the migration and invasion of gastric cancer cells in vitro and enhanced tumor metastasis in nude mice model. Mechanism studies revealed that eIF4A1 induced epithelial-to-mesenchymal transition (EMT) of gastric cancer cells through driving the translation of SNAI1 mRNA. Together, these findings indicate that eIF4A1 promotes EMT and metastasis of gastric cancer and suggest that eIF4A1 is a potential target for the adjuvant therapy for gastric cancer patients.

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MBP-1 Suppresses Growth and Metastasis of Gastric Cancer Cells through COX-2

Molecular Biology of the Cell ◽

10.1091/mbc.e09-05-0386 ◽

2009 ◽

Vol 20 (24) ◽

pp. 5127-5137 ◽

Cited By ~ 27

Author(s):

Kai-Wen Hsu ◽

Rong-Hong Hsieh ◽

Chew-Wun Wu ◽

Chin-Wen Chi ◽

Yan-Hwa Wu Lee ◽

...

Keyword(s):

Gastric Cancer ◽

Tumor Progression ◽

Cancer Cells ◽

Cancer Progression ◽

Epithelial Mesenchymal Transition ◽

Suppressive Effect ◽

Migration And Invasion ◽

Gastric Cancer Cells ◽

Mesenchymal Transition ◽

Cox 2

The c-Myc promoter binding protein 1 (MBP-1) is a transcriptional suppressor of c-myc expression and involved in control of tumorigenesis. Gastric cancer is one of the most frequent neoplasms and lethal malignancies worldwide. So far, the regulatory mechanism of its aggressiveness has not been clearly characterized. Here we studied roles of MBP-1 in gastric cancer progression. We found that cell proliferation was inhibited by MBP-1 overexpression in human stomach adenocarcinoma SC-M1 cells. Colony formation, migration, and invasion abilities of SC-M1 cells were suppressed by MBP-1 overexpression but promoted by MBP-1 knockdown. Furthermore, the xenografted tumor growth of SC-M1 cells was suppressed by MBP-1 overexpression. Metastasis in lungs of mice was inhibited by MBP-1 after tail vein injection with SC-M1 cells. MBP-1 also suppressed epithelial-mesenchymal transition in SC-M1 cells. Additionally, MBP-1 bound on cyclooxygenase 2 (COX-2) promoter and downregulated COX-2 expression. The MBP-1-suppressed tumor progression in SC-M1 cells were through inhibition of COX-2 expression. MBP-1 also exerted a suppressive effect on tumor progression of other gastric cancer cells such as AGS and NUGC-3 cells. Taken together, these results suggest that MBP-1–suppressed COX-2 expression plays an important role in the inhibition of growth and progression of gastric cancer.

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