High Expression of GRP78 Promotes Invasion and Metastases in Patients with Esophageal Squamous Cell Carcinoma

Esophageal squamous cell carcinoma (ESCC) has a poor prognosis due to its high frequency of metastasis and invasion. Recent studies have suggested glucose-regulated protein 78KD (GRP78) may play important roles in progression and development of malignant tumors. However, the mechanisms of invasion and metastasis of ESCC in relation to GRP78 still remain obscure. The aim of this study was to investigate the effect of GRP78 on invasion and metastasis of ESCC and to explore its potential mechanism. GRP78 expression levels in ESCC tissues were examined by immunohistochemistry. RT-PCR and western blot were used to test the relative expression of GRP78 in non-metastatic and high-metastatic ESCC cells. In vitro and in vivo studies were both performed to investigate the role of GRP78 in invasion and metastasis of ESCC cells. The expression of metastasis-related proteins was examined by western blot in GRP78-depleted cells. The expression of GRP78 is correlated with invasion, metastasis and poor prognosis in ESCC patients. GRP78 expression was significantly higher in highly metastatic cells compared with ESCC non-metastatic cells. In addition, down-regulation of GRP78 significantly inhibited the metastatic potential of ESCC cells in both in vitro and in vivo studies. The expression of MMP-2 and MMP-9 were down-regulated in GRP78-depleted ESCC cells. The present study demonstrated that GRP78 plays important roles in invasion and metastasis of ESCC, indicating that GRP78 might be used as a potential prognostic and therapeutic marker in patients with ESCC by modulating the expression of MMP-2 and MMP-9.