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

Authors

  • Yu Su,

    1. Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Peking University Center for Human Disease Genomics, Beijing, China
    2. Key Laboratory of Medical Immunology, Ministry of Health, Beijing, China
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    • These authors contributed equally to this work.
  • Yi Lin,

    1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
    2. Department of Surgery, Peking University Cancer Hospital and Institute, Beijing, China
    3. Department of General Surgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
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    • These authors contributed equally to this work.
  • Lianhai Zhang,

    1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
    2. Department of Surgery, Peking University Cancer Hospital and Institute, Beijing, China
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  • Baocai Liu,

    1. Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Peking University Center for Human Disease Genomics, Beijing, China
    2. Key Laboratory of Medical Immunology, Ministry of Health, Beijing, China
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  • Wanqiong Yuan,

    1. Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Peking University Center for Human Disease Genomics, Beijing, China
    2. Key Laboratory of Medical Immunology, Ministry of Health, Beijing, China
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  • Xiaoning Mo,

    1. Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Peking University Center for Human Disease Genomics, Beijing, China
    2. Key Laboratory of Medical Immunology, Ministry of Health, Beijing, China
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  • Xiaohong Wang,

    1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
    2. Clinical Gastric Cancer Research Laboratory, Peking University Cancer Hospital and Institute, Beijing, China
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  • Henan Li,

    1. Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Peking University Center for Human Disease Genomics, Beijing, China
    2. Key Laboratory of Medical Immunology, Ministry of Health, Beijing, China
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  • Xiaofang Xing,

    1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
    2. Clinical Gastric Cancer Research Laboratory, Peking University Cancer Hospital and Institute, Beijing, China
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  • Xiaojing Cheng,

    1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
    2. Clinical Gastric Cancer Research Laboratory, Peking University Cancer Hospital and Institute, Beijing, China
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  • Bin Dong,

    1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
    2. Department of Pathology, Peking University Cancer Hospital and Institute, Beijing, China
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  • Ying Hu,

    1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
    2. Department of Tissue Bank, Peking University Cancer Hospital and Institute, Beijing, China
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  • Hong Du,

    1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
    2. Department of Tissue Bank, Peking University Cancer Hospital and Institute, Beijing, China
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  • Yubing Zhu,

    1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
    2. Department of Surgery, Peking University Cancer Hospital and Institute, Beijing, China
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  • Ning Ding,

    1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
    2. Department of Surgery, Peking University Cancer Hospital and Institute, Beijing, China
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  • Jiyou Li,

    1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
    2. Department of Pathology, Peking University Cancer Hospital and Institute, Beijing, China
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  • Weili Liu,

    1. Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Peking University Center for Human Disease Genomics, Beijing, China
    2. Key Laboratory of Medical Immunology, Ministry of Health, Beijing, China
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  • Yongzhen Ma,

    1. Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Peking University Center for Human Disease Genomics, Beijing, China
    2. Key Laboratory of Medical Immunology, Ministry of Health, Beijing, China
    3. Department of Histology and Embryology, Shandong Medical College, Linyi City, China
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  • Xiaoyan Qiu,

    1. Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Peking University Center for Human Disease Genomics, Beijing, China
    2. Key Laboratory of Medical Immunology, Ministry of Health, Beijing, China
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  • Jiafu Ji,

    Corresponding author
    1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
    2. Department of Surgery, Peking University Cancer Hospital and Institute, Beijing, China
    • Jiafu Ji, Department of Surgery, Peking University Cancer Hospital & Institute, 52 Fucheng Road, Beijing 100142, China.

      Tel: +86-10-8819-6048; Fax: +86-10-8819-6698;

      E-mail: jiafuj@gmail.com

      Wenling Han, Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, China.

      Tel: +86-10-8280-5479; Fax: +86-10-8280-1149;

      E-mail: hanwl@bjmu.edu.cn

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  • Wenling Han

    Corresponding author
    1. Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Peking University Center for Human Disease Genomics, Beijing, China
    2. Key Laboratory of Medical Immunology, Ministry of Health, Beijing, China
    • Jiafu Ji, Department of Surgery, Peking University Cancer Hospital & Institute, 52 Fucheng Road, Beijing 100142, China.

      Tel: +86-10-8819-6048; Fax: +86-10-8819-6698;

      E-mail: jiafuj@gmail.com

      Wenling Han, Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, China.

      Tel: +86-10-8280-5479; Fax: +86-10-8280-1149;

      E-mail: hanwl@bjmu.edu.cn

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Abstract

The CKLF-like MARVEL transmembrane domain containing 3 (CMTM3) gene is a novel tumor suppressor with frequent epigenetic inactivation. In this study, we showed the role played by CMTM3 in gastric cancer cells as a tumor suppressor gene, and examined the correlation between CMTM3 expression and clinicopathological parameters using immunohistochemistry in gastric cancer patients with different pathological stages (n = 350). We found that CMTM3 expression was reduced or silenced by epigenetic regulation in gastric cell lines, and dramatically downregulated in primary gastric cancer tissues. Restoration of CMTM3 significantly affected migration and invasion of AGS and SGC-7901 cells (< 0.001). In vivo experiments showed that peritoneal disseminated metastases were significantly suppressed by CMTM3 (< 0.001). We further showed that the expression of MMP2 and the phosphorylation of Erk1/2 were decreased when CMTM3 was restored. In addition, by immunohistochemical staining, we found that the expression of CMTM3 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, CMTM3 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 CMTM3 regulates migration and invasion of gastric cancer cells. Moreover, CMTM3 is a candidate marker for prognosis of gastric cancer in the clinic.

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