The Diagnostic and Therapeutic Potential of Cell Differentiation-Related Gene DLK1/Pref-1 in Ovarian Cancer

DLK1/Pref-1, a transmembranous protein belonging to the epidermal growth factor (EGF)-like superfamily, was initially identified as secreted factor that inhibit adipogenesis. Recently, emerging evidences support its role in cell differentiation and the relationship between DLK1/Pref-1 and tumorigenesis is also noted. DLK1/Pref-1 has been reported to express in tumors with neuroendocrine features, hepatoblastoma, and a subset of hepatoma. The search of Human Protein Atlas website reveals ovarian cancer is the fourth most frequent cancer with DLK1/Pref-1 expression, only next to endometrial cancer, glioma and liver cancer. In the previous study, we have found that an elevated DLK1/Pref-1 protein level in advanced ovarian cancer cells. Gene transfer studies were performed to elucidate the influence of cellular DLK1 level on the malignant behavior of ovarian cancer cells. Adenovirus-mediated DLK1 over-expression stimulated the motility, colony formation, and invasiveness of JH514 cells. Conversely, DLK1 knockdown by RNA interference in A2780 and SKOV-3 cells attenuated the malignant behavior. Accordingly, we propose to study the role of DLK1/Pref-1 in ovarian adenocarcinomas in this 3-year project as follows: 1) DLK1/Pref-1 expression on oncogenic mechanisms and signaling pathway of ovarian cancer. (1st Year) 2) DLK1/Pref-1 expression on ovarian adenocarcinoma xenograft model in athymic nude mice (2nd Year) 3) DLK1/Pref-1 expression on chemoresistance and cancer stemness of ovarian cancer (3rd Year) The results from this study would be helpful to clarify the prognostic role of DLK1/Pref-1 as well as the oncogenic function of DLK1/Pref-1 in ovarian carcinogenesis. Moreover, the information will assist the development of anti-cancer strategies for the treatment of ovarian adenocarcinomas in the future.

Project ID:PC10308-0652
External Project ID:MOST103-2320-B182-005-MY3