Dissected the Role of Glucose-Regulated Protein 94 (GRP94),The Clinically Therapeutic Implication and Drug Development in Colon Cancer

Cancer has been the leading cause of death in Taiwan for nearly the past 30 years. Colorectal cancer is the 3rd most common cancer and 3rd leading cause of cancer death in western countries. Since 2006, more than 10,000 patients have been diagnosed with colorectal cancer annually. Colorectal cancer has become the most commonly diagnosed malignancy in Taiwan and is also the 3rd leading cause of cancer death (10%). The local recurrence and distant metastasis, to locations such as liver and lung, are the major causes of colorectal cancer-related death. Tumor over-growth or radiation resistance is the reason for local recurrence, and chemo-resistance is the cause of distant metastasis. Thus, understanding the mechanism for tumor growth, metastasis and treatment resistance is an important issue. 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 colorectal cancer is still unclear. To understand the role of GRP94 in colorectal cancer, we tried to knock down the expression of GRP94 in colon 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 DLD-1 cells. Those preliminary results demonstrated that GRP94 may play an important role in colon cancer progression and metastasis. Here, we plan to further dissect the role of GRP94 in colon cancer. Further, we plan to dissect the role of GRP94 in chemo-resistant and irradiation resistant colon cancer. We believe that ER stress-related proteins could become an important target in the diagnosis or monitoring the therapeutic efficacy in colon cancer.