Oral squamous cell carcinoma represents more than 90% head and neck cancers with high incidence rate and morbidity. To date, little is known about the molecular mechanisms responsible for OSCC initiation and progression to advanced disease. Thus, identifying key pathways involved in OSCC pathobiology is likely to lead to the identification of new druggable targets and future anti-cancer therapies.
Work from our laboratory has linked the metabolic pathway of protein N-glycosylation with OSCC biology. Specifically, overexpression of the first N-glycosylation gene, DPAGT1, in human OSCC tumor specimens was shown to be associated with aberrant activation of canonical Wnt signaling and inhibition of mature E-cadherin junctions. The purpose of this study was to examine how increased N-glycosylation was associated with OSCC growth and metastatic properties in cellular and murine models. We show that high level of DPAGT1 expression correlates with increased cell surface modification of malignant OSCC HSC-3 cells with complex N-glycans. Further, HSC-3 cells are hypersenitive to the N-glycosylation inhibitor, tunicamycin, suggesting that aggressive properties of OSCC cells depend, in part, on the N-glycosylation pathway. Lastly, we show that orthotopic HSC-3 cell-derived tumor xenografts are inhibited by tunicamycin both in overall growth and metastases, indicating that targeting DPAGT1 and N-glycosylation may represent a new strategy for the treatment of OSCC in human patients.
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/26378 |
| Date | 25 October 2017 |
| Creators | Bukhari, Samah |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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