Original paper

Clinical & Experimental Metastasis

, Volume 23, Issue 7, pp 401-410

Association of elevated GRP78 expression with increased lymph node metastasis and poor prognosis in patients with gastric cancer

  • Jun ZhangAffiliated withDepartment of Gastrointestinal Medical Oncology, Unit 426, M. D. Anderson Cancer Center, The University of Texas
  • , Yixing JiangAffiliated withDepartment of Gastrointestinal Medical Oncology, Unit 426, M. D. Anderson Cancer Center, The University of Texas
  • , Zhiliang JiaAffiliated withDepartment of Gastrointestinal Medical Oncology, Unit 426, M. D. Anderson Cancer Center, The University of Texas
  • , Qiang LiAffiliated withDepartment of Gastrointestinal Medical Oncology, Unit 426, M. D. Anderson Cancer Center, The University of Texas
  • , Weida GongAffiliated withDepartment of Neurosurgery, M. D. Anderson Cancer Center, The University of Texas
  • , Liwei WangAffiliated withShanghai East Hospital Cancer Center, Tongji University
  • , Daoyan WeiAffiliated withDepartment of Gastrointestinal Medical Oncology, Unit 426, M. D. Anderson Cancer Center, The University of Texas
  • , James YaoAffiliated withDepartment of Gastrointestinal Medical Oncology, Unit 426, M. D. Anderson Cancer Center, The University of Texas
  • , Shengyun FangAffiliated withMedical Biotechnology Center, University of Maryland Biotechnology Institute
    • , Keping XieAffiliated withDepartment of Gastrointestinal Medical Oncology, Unit 426, M. D. Anderson Cancer Center, The University of Texas Email author 

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Abstract

Glucose-regulated protein 78 (GRP78) has been implicated in the protection of tumor cells from cytotoxic damage and apoptosis and thus assists cells in survival under oxygen-deprivation and nutrient-stress conditions. However, its expression and potential role in gastric cancer development and progression have not been reported. In the present study, we determined the level of GRP78 expression in the primary tumor in 86 cases of resected gastric cancer by using immunohistochemistry and analyzed the relationships between GRP78 and clinicopathological characteristics. We found that GRP78 was overexpressed in the tumor specimens when compared with the expression in adjacent tumor-free gastric mucosa. Furthermore, the level of GRP78 expression in both primary tumors and metastatic lymph nodes was inversely correlated with patient survival. Overexpression of GRP78 was directly correlated with Sp1 expression and increased lymph node metastasis. Knocking down GRP78 expression inhibited tumor cell invasion in vitro and growth and metastasis in a xenograft nude mouse model. Therefore, our data imply that dysregulated expression of GRP78 may contribute to the development and progression of gastric cancer.

Keywords

Prognosis Transcription factor Invasion Metastasis Stomach