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

RIP2 在 NF-κB 激活和 XIAP 诱导转移调节中的作用

• 批准号: 230779395
• 负责人: Professor Dr. Andreas Krieg
• 金额: --
• 依托单位: Klinik für Allgemein-, Viszeral- und Kinderchirurgie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2012
• 资助国家: 德国
• 起止时间: 2011-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/230779395?language=en
• 关键词: Role; RIP2; activation; NF; kappaB

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.

结直肠癌是西欧肿瘤相关死亡的第二大原因。独立于诊断工具和手术策略，即使针对转移性疾病，主要的困境仍然是肿瘤复发和转移性疾病的发展，其分子机制尚不完全清楚。最近，一组抗凋亡蛋白，即凋亡蛋白抑制剂（IAP）家族，因其抑制细胞死亡诱导的半胱天冬酶而受到关注。XIAP是该家族中最著名的成员之一，其特点是具有抗凋亡特性以及作为转录因子NF-kappaB激活剂的功能。因此，已知NF-kappaB诱导的信号通路在肿瘤发生和转移中起着至关重要的作用。本项目旨在阐明xiap诱导的NF-kappaB激活在结直肠癌肿瘤进展中的分子机制。在这种情况下，中心目标之一是显示接头蛋白RIP2和TAB1与xiap诱导的NF-kappaB激活的相关性。因此，这些RIP2、TAB1和XIAP之间的分子和功能相互作用的数据可能为结直肠癌的治疗策略提供新的见解。