Determined the Role and the Mechanims of GRP94 in Mediating the Progression and Therapeutic Responses of HCC

Liver cancer is the most important and leading causes of cancer death for people in Taiwan. Several studies showed that the endoplasmic reticulum stress related proteins glucose-regulated protein 94 (GRP94) was correlated the cancer progression and therapeutic response in deferent cancers. However, the role of GRP94 in progression and therapeutic response in HCC cancer is still unclear. In order to understand the role of GRP94 in HCC, we tried to knockdown the expression of GRP94 in HCC cells (HepJ5, Mahlavu, and skHep-1 cells). To verify the proliferatory and migratory ability, we found that silenced of GRP94 cause the reduction the proliferation activity and migratory ability in those cells. To further confirm those results in xenograft model, we confirmed that silencing GRP94 reduced the tumor formation. Those results demonstrated that GRP94 may play important role in HCC progression and metastasis. In order to realize the mechanism, we performed the Nanostrip analysis and found that silencing altered several different pathways involving in cell growth and metastasis. We will further analyze the regulation between GRP94 and those pathways. Besides, we planned to dissect the role of GP96 in chemo-resistant and irradiated resistant of HCC and screening the drug which can suppress the GRP94 levels. We believe that ER-stress related protein may become an important target in monitoring the HCC diagnostic or therapeutic efficacy.