Cell biological characterization of EBAG9/RCAS1 as a modifier of tumor-associated O-linked glycan expression

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Aberrant glycan epitopes are appreciated as a hallmark of essentially all types of experimental and human cancers. The O-linked blood group precursor structures TF (Thomsen-Friedenreich) and Tn have received particular attention because they are normally cryptic and they occur on a variety of tumor cells. They result from incomplete O-glycan synthesis and are occluded from the immune system by glycan extension and sialylation. Functionally, TF and Tn are thought to be involved in tumor cell adhesion, invasion, and metastasis. The mechanisms that contribute to their occurrence in tumors remain poorly understood. We have recently characterized a tumor-associated antigen, EBAG9, which caused the deposition of Tn and TF on cell lines. The identification of the SNAREassociated molecule Snapin as an interaction partner pointed to an involvement of EBAG9 in the control of the secretory pathway. Here, we will apply a multidisciplinary approach to study the pathways and functional consequences of EBAG9-related O-linked glycan expression. We will test the hypothesis if EBAG9 has a more general role in the regulation of diverse vesicle trafficking routes and if this function can provide a link between tumor pathogenesis and deregulation of EBAG9 expression in some tumor entities. In conclusion, this application is aimed at the development of an integrated conceptual framework for vesicle transport, O-linked glycan synthesis, and tumor pathogenesis.