Functional Characterization of Nsfl1c in Oral Cancer Using Quantitative Proteomics

Oral cavity squamous cell carcinoma (OSCC) is the fifth cause of cancer-related death and results in more than 2500 deaths per year in Taiwan. Despite remarkable advances in treatment during the past decade, approximately 50% of OSCC patients die within 5 years after initial diagnosis, mostly ascribed to lymphatic metastasis or local recurrence. Indeed, five-year survival rate of OSCC patients with lymphatic metastasis is less than 40%, compared to 90% of patients without metastasis. Thus, it is important to identify metastasis-associated molecules to develop strategies for attenuation of lymphatic metastasis and tailored therapies of individual patients. Toward this end, the proteome of tissue interstitial fluids from tumor (TIF) and adjacent non-cancerous tissues (NIF) in oral cavities has been quantitatively profiled. Among the identified proteins, NSFL1 cofactor p47 (NSFL1C or p47), has been selected for further investigation, based on the findings that the level of NSFL1C in TIFs is higher than that in NIFs, and noteworthily, its level in TIFs collected from lymph-node metastatic OSCC is significantly elevated comparing with that without the metastasis. NSFL1C is intimately known to be involved in the reassembly of Golgi stacks at the end of mitosis through the interaction with valosin-containing protein (p97/VCP), a cytosolic ATPase associated with various cellular activities. However, the expressional profiling and the function of NSFL1C in human cancers remain limited to date. Our preliminary data have revealed that NSFL1C, as a migration-promoting protein in OSCC cells, is over-expressed in OSCC tissues compared to adjacent non-cancerous counterparts. Given that OSCC is a highly metastatic head and neck cancer, deciphering the mechanism underlying the NSFL1C-mediated metastasis in OSCC will accelerate the understanding of OSCC progression. In the present proposal, using quantitative proteomics technology, we attempt to (1) comprehensively identify the components of NSFL1C-associated protein complexes and (2) discover the proteins which are potentially regulated by NSFL1C. The candidates selected from (1) and (2) will be evaluated for their roles in regulation of NSFL1C-mediated promotion of cell migration. 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:PC10607-0344
External Project ID:MOST106-2320-B182-021