The Role of RIP2 in activation of NF-kappaB and regulation of XIAP-induced metastasis

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Colorectal Cancer is the second leading cause of tumor related deaths in western europe. Independently of diagnostic tools and operative strategies, even against metastatic disease, the main dilemma remains the development of tumor recurrence and metastasizing disease, of which the molecular mechanism are not completely understood.Recently, a group of antiapototic proteins, the inhibitor of apoptosis protein (IAP) family, attracted attention due to their inhibition of cell death inducing caspases. XIAP is one of the best known members of this family characterized by its antiapoptotic properties as well as its function as activator of the transcription factor NF-kappaB. Thus it is known, that NF-kappaB induced signaling pathways play a crucial role in tumorigenesis and metastasis.Aim of the presented project is to elucidate the molecular mechanisms of XIAP-induced NF-kappaB activation in tumor progression in colorectal cancers. In this context, one of the central aims is to show the relevance of both adaptor proteins RIP2 and TAB1 for XIAP-induced NF-kappaB activation. Thus, these data of the molecular and functional interaction between RIP2, TAB1 and XIAP might provide new insights for therapeutical strategies in colorectal cancer.