Abstract 1540: Midkine-raised oral cancer growth, migration and invasion is required for RBPJk modulation

Oral squamous cell carcinoma (OSCC) represents 95% of all forms of head and neck cancer, and its incidence has increased by 50% during the past decade. Despite the nowadays available therapeutic managements, such as surgery, radiotherapy, chemotherapy or in combination, the five-year survival rate is still improved. The current view is to present that the accumulations of genetic and epigenetic alterations in OSCC lead to the progression of cancer. Our previous study indicated that midkine, heparin-binding growth factor, was overexpressed in tumor tissues of head and neck cancer patients and its expression also correlated with poor 5-year survival. In this study, we tried to explore the biological functions and mechanisms of midkine in vitro and in vivo. Established gain-of-function of midkine in two oral cancer cell lines not only promoted cell growth by MTT, soft agar and BrdU assays, but also induced tumor growth in xenograft model. Midkine-overexpressing cells induced cell migration and invasion by wound healing and Transwell assays. Conversely, cell growth, migration and invasion were also inhibited; while endogenous midkine was abolished by midkine-mediated siRNA in oral cancer cells. By using bioinformatics, Q-RT-PCR, Western blotting, promoter assay and ChIP assay, we identified that RBP-Jk, a transcriptional factor, could bind to the promoter regions of midkine and to induce midkine expression in oral cancer cells. In the specimens of oral cancer patients, the expressions of midkine and RBP-Jk had a positive correlation by immunohistochemistry. Taken together, these results demonstrated that RBP-Jk regulates midkine expression and involves in midkine-elicited tumor formation in oral cancer. Citation Format: Tai-Jan Chiu, Yi-Ching Chen, Chang-Han Chen. Midkine-raised oral cancer growth, migration and invasion is required for RBPJk modulation. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1540.