Characterization of Nsfl1c Role in Oral Cancer Metastasis with Interactome Analysis

In Taiwan, oral cancer is the fifth leading cause of cancer-related mortality and has brought about 2936 deaths in 2016. Despite advances in oral cancer treatment, approximately 50% of patients die within 5 years after initial diagnosis, mostly ascribed to lymphatic metastasis of cancer cells. Five-year survival rate of oral cancer patients with lymphatic metastasis is less than 40% compared with 90% of patients without metastasis, suggesting that it is needed to identify biomarkers and therapeutic targets for diagnosis and treatment of oral cancer metastasis. We consider that NSFL1 cofactor p47 (NSFL1C or p47) is a potential therapeutic target of oral cancer metastasis, based on the findings that the NSFL1C level in tissue interstitial fluids of oral cancer is higher than that in non-cancerous tissue interstitial fluids, and noteworthily, NSFL1C level in tissue interstitial fluids of oral cancer with lymphatic metastasis is significantly elevated compared with that without lymphatic metastasis. NSFL1C is involved in the reassembly of Golgi stacks at the end of mitosis via the interaction with valosin-containing protein (p97/VCP), a cytosolic ATPase associated with various cellular activities. However, its expressional profiles and functions in cancers remain limited to date. Our preliminary data have revealed that NSFL1C is over-expressed in oral cancer tissues compared to adjacent non-cancerous counterparts, and plays a promoting role in oral cancer cell migration and invasion. Given that oral cancer is a highly metastatic head and neck cancer, deciphering the mechanism underlying the NSFL1C-mediated metastasis will accelerate the understanding of oral cancer progression. In the present proposal, we attempt to (1) comprehensively identify the components of NSFL1C-associated protein complexes, and (2) functionally characterize the role of NSFL1C-interacting partners in NSFL1C-mediated promotion of cell migration and cancer metastasis. The therapeutic potential (3) of NSFL1C and NSFL1C-associated pathway will be further evaluated in cell and mouse xenograft models. This study will not only provide the novel insights of NSFL1C in cancer formation and progression, but also lead to therapeutic targets to limit the spreading of oral cancer.

Project ID:PC10707-0099
External Project ID:MOST107-2320-B182-009