CMTM3 inhibits cell migration and invasion and correlates with favorable prognosis in gastric cancer
Yu
Su1,
Yi
Lin2,
Lianhai
Zhang2,
Baocai
Liu1,
Xiaohong
Wang2,
Henan
Li1,
Xiaofang
Xing2,
Xiaojing
Cheng2,
Bin
Dong2,
Ying
Hu2,
Hong
Du2,
Ying-ai
Li2,
Yubing
Zhu2,
Ning
Ding2,
Jiyou
Li2,
Weili
Liu1,
Yongzhen
Ma1,
Xiaoyan
Qiu1,
Dalong
Ma1,
Jiafu
Ji2* and
Wenling
Han1*
-
1
Peking University Health Science Center, China
-
2
Peking University Cancer Hospital & Institute, China
CKLF-like MARVEL transmembrane domain containing 3 (CMTM3) is a novel tumor suppressor gene (TSG) with frequent epigenetic inactivation by promoter CpG methylation. In this study, we demonstrated the roles played by CMTM3 in gastric cancer cells as a TSG, and examined the correlation between CMTM3 expression and clinicopathological parameters by immunohistochemistry in gastric cancer patients with different pathological stages (n = 350). We found that CMTM3 expression was reduced or silenced by methylation in several gastric cell lines, and restoration of CMTM3 significantly affected migration and invasion of AGS and SGC-7901 cells (P < 0.001). In vivo experiments showed that peritoneal disseminated metastases were significantly suppressed by CMTM3 (P < 0.001). We further showed that the expression of MMP2 and the phosphorylation of Erk1/2 was decreased when CMTM3 restoration, suggesting the potential mechanism of the tumor suppressor effect caused by CMTM3 in gastric cancer cells. In addition, the expression of CMTM3 was remarkably weaker in gastric cancer tissues than that in normal mucosa (P = 0.008), and was significantly correlated with Gender (P = 0.033), Tumor Depth (P = 0.049), Stage (P = 0.021), Histologic Grade (P = 0.022). More importantly, CMTM3 expression was associated with prognosis in gastric cancer patients (P = 0.041), and was a significant independent prognostic indicator (HR = 0.704, 95%CI, 0.498 to 0.994; P = 0.046). Our findings indicate that CMTM3 regulates migration and invasion of gastric cancer cells. Moreover, CMTM3 is a candidate marker for prognosis of gastric cancer in clinic.
Acknowledgements
This study was supported by the National Key Technology R&D Program (2011ZX09307-001-05) and National Natural Science Foundation of China (30972780).
Keywords:
CMTM3,
MARVEL,
tumor suppressor gene,
gastric cancer,
Survival
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Immune-mediated disease pathogenesis
Citation:
Su
Y,
Lin
Y,
Zhang
L,
Liu
B,
Wang
X,
Li
H,
Xing
X,
Cheng
X,
Dong
B,
Hu
Y,
Du
H,
Li
Y,
Zhu
Y,
Ding
N,
Li
J,
Liu
W,
Ma
Y,
Qiu
X,
Ma
D,
Ji
J and
Han
W
(2013). CMTM3 inhibits cell migration and invasion and correlates with favorable prognosis in gastric cancer.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00484
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Received:
27 Mar 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Jiafu Ji, Peking University Cancer Hospital & Institute, Beijing, China, jiafuj@gmail.com
Dr. Wenling Han, Peking University Health Science Center, Beijing, China, hanwl@bjmu.edu.cn