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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.

CMTM3 inhibits cell migration and invasion and correlates with favorable prognosis in gastric cancer