Dissected the Role of Glucosed-Regulated Portein 78 in the Progression, Metastasis and Therapy of Colorectal Cancer

Cancer is the first leading cause of death in Taiwan for the past near 30 years. Colorectal cancer is the 3rd common cancer and 3rd leading cause of cancer death in western country. Since 2006, there were more than 10000 patients with colorectal cancer were diagnosed annually and the colorectal cancer became the most common diagnosed malignancy in Taiwan which is also the 3rd leading cause of cancer death (10%). The local recurrence and distant metastasis such as liver and lung metastasis are the major causes of the colorectal cancer death. The tumor over-growth or radiation resistance is the reason for local recurrence and the chemo-resistance is the cause of distant metastasis. So understand of mechanism for tumor growth, metastasis and treatment resistance is an important issue. The glucose-regulated protein 78 (GRP 78) is one of endoplasmic reticulum (ER) chaperones originally discovered as proteins inducible by glucose starvation. GRP 78 participates in ER protein translocation, chaperoning, protein quality control, ER-associated protein degradation, ER stress sensing and regulation, and ER calcium binding. When the cells were in the critical environment such as glucose deprivation, the GRP 78 would be over-expressed. Recently, the endoplasmic reticulum stress pathways and the GRPs have been linked to cancer growth and drug resistance. In the past, only few studies focusing on GRP78 and colorectal cancer were reported. So, we try to demonstrate the influence of GRP78 on colorectal cancer behavior (proliferation and migration) and the relationship between GRP78 and effect of colorectal cancer treatment. Our preliminary results demonstrated that silenced GRP78 may influence the cancer formation, progression, metastasis and therapeutic responses. We believe that GRP78 may be the prognostic and diagnostic marker for colorectal cancer.