Studied the Roles of Grp94 in the Progression and Metastasis of Esophageal Squamous Carcinoma, Mechanism Dissection, and Drug Development

Project: A - Government Institutionb - Ministry of Science and Technology

Description

Esophageal cancer, an aggressive upper gastrointestinal malignancy, is estimated to be among the 10 most common malignancies worldwide. The prognosis for esophageal cancer is relatively poor, with a 5-year survival rate of less than 20%. In Taiwan, esophageal cancer is the seventh most common cancer and the sixth leading cause of cancer-related death in males. Esophageal cancer exists as two different histological types: squamous cell carcinoma (SCC) and adenocarcinoma. More than 90% of patients with esophageal cancer in Taiwan are SCC. Unfortunately, patients are often diagnosed with esophageal cancer at an advanced stage; therefore, limited or no effective therapies are available. Endoplasmic reticulum stress, which results from protein misfolding within the secretory pathway, has a profound effect on cancer cell proliferation and survival. The glucose-regulated proteins (GRPs) are stress-inducible chaperones that mostly reside in the endoplasmic reticulum or the mitochondria. Several studies have shown that the endoplasmic reticulum stress-related protein glucose-regulated protein 94 (GRP94) was correlated to cancer progression and the therapeutic response in different cancers.However, the role of GRP94 in the progression and therapeutic response in esophageal cancer is still unclear. To understand the role of GRP94 in esophageal cancer, we tried to knock down the expression of GRP94 in esophageal cancer cell lines. To verify the proliferative and migratory ability, we found that silencing GRP94 causes the reduction of proliferation activity and migratory ability in CE81T cells. In addition, the overexpression of GRP94 also correlated to the worst outcome of human esophageal cancer patients. Those results show that GRP94 indeed plays important role in the progression of esophageal cancer. Therefore, we propose that GRP94 may be a predictive factor for the progression and therapeutic response for chemotherapy or radiation therapy on esophageal cancer. In addition, we will develop the new drugs through targeting GRP-94 by GENEDOCK in this study. We believe our study may provide the new information for the prognostic and diagnostic for esophageal cancer and increase the therapeutic efficacy for esophageal cancer in future.
StatusFinished
Effective start/end date8/1/167/31/17