Open AccessCMTM3 inhibits cell migration and invasion and correlates with favorable prognosis in gastric cancer
Author(s) -
Su Yu,
Lin Yi,
Zhang Lianhai,
Liu Baocai,
Yuan Wanqiong,
Mo Xiaoning,
Wang Xiaohong,
Li Henan,
Xing Xiaofang,
Cheng Xiaojing,
Dong Bin,
Hu Ying,
Du Hong,
Zhu Yubing,
Ding Ning,
Li Jiyou,
Liu Weili,
Ma Yongzhen,
Qiu Xiaoyan,
Ji Jiafu,
Han Wenling
Publication year - 2014
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12304
Subject(s) - immunohistochemistry , cancer , medicine , cancer cell , pathological , epigenetics , cancer research , pathology , hazard ratio , biology , confidence interval , gene , biochemistry
The CKLF ‐like MARVEL transmembrane domain containing 3 ( CMTM 3 ) gene is a novel tumor suppressor with frequent epigenetic inactivation. In this study, we showed the role played by CMTM 3 in gastric cancer cells as a tumor suppressor gene, and examined the correlation between CMTM 3 expression and clinicopathological parameters using immunohistochemistry in gastric cancer patients with different pathological stages ( n = 350). We found that CMTM 3 expression was reduced or silenced by epigenetic regulation in gastric cell lines, and dramatically downregulated in primary gastric cancer tissues. Restoration of CMTM 3 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 CMTM 3 ( P < 0.001). We further showed that the expression of MMP 2 and the phosphorylation of Erk1/2 were decreased when CMTM 3 was restored. In addition, by immunohistochemical staining, we found that the expression of CMTM 3 was remarkably weaker in gastric cancer tissues than in normal mucosae ( P = 0.008), and was significantly correlated with gender ( P = 0.033), tumor depth ( P = 0.049), stage ( P = 0.021), and histological grade ( P = 0.022). More importantly, CMTM 3 expression was associated with prognosis in gastric cancer patients ( P = 0.041), and was a significant independent prognostic indicator (hazard ratio = 0.704, 95% confidence interval, 0.498–0.994; P = 0.046). Our findings indicate that CMTM 3 regulates migration and invasion of gastric cancer cells. Moreover, CMTM 3 is a candidate marker for prognosis of gastric cancer in the clinic.