Association of elevated GRP78 expression with increased lymph node metastasis and poor prognosis in patients with gastric cancer.
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.
Zhang
Jun
J
Department of Gastrointestinal Medical Oncology, Unit 426, M. D. Anderson Cancer Center, The University of Texas, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Jiang
Yixing
Y
Jia
Zhiliang
Z
Li
Qiang
Q
Gong
Weida
W
Wang
Liwei
L
Wei
Daoyan
D
Yao
James
J
Fang
Shengyun
S
Xie
Keping
K
D000328:Adult; D000368:Aged; D000818:Animals; D045744:Cell Line, Tumor; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D006360:Heat-Shock Proteins / Q000032:analysis* / Q000502:physiology; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D018832:Molecular Chaperones / Q000032:analysis* / Q000502:physiology; D009361:Neoplasm Invasiveness; D011379:Prognosis; D016329:Sp1 Transcription Factor / Q000032:analysis; D013274:Stomach Neoplasms / Q000737:chemistry / Q000401:mortality / Q000473:pathology*
D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D018832:Molecular Chaperones; D016329:Sp1 Transcription Factor