| セッション情報 | The 2nd JSGE International Topic Conference4）Inflammation and Carcinogenesis in the Intestine（Part1） |
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| タイトル | IT4-2：The Role of IKKb-dependent NF-kB Signaling on Different Stages of Intestinal Carcinogenesis |
| 演者 | Schwitalla Sarah（Institute of Molecular Immunology, Technical University Munich, Germany） |
| 共同演者 | Greten Florian |
| 抄録 | Persistent activation of NF- kB has been observed in a variety of tumor tissues including colorectal cancer but its specific function is only poorly understood. One of the first steps during tumor initiation is attributed to mutations in the Wnt pathway. By means of a mouse model having an epithelial specific mutation in the Ctnnb gene leading to a constitutively active Wnt pathway and crypt stem cell expansion, NF-kB was shown to modulate aberrant Wnt signaling on the promoter level. While deletion of NF-kB delays cell transformation, conversely enhanced NF-kB activity promoted the phenotype and resulted in the formation of foci displaying stem cell characteristics in aberrant position. Generating a new mouse model proved that post-mitotic cells can dedifferentiate in vivo to acquire tumor-initiating properties. During the course of tumor development additional mutations in oncogenes or tumor suppressive genes such as Tp53 are required for tumor progression resulting in increased tumor incidence and spontaneous colorectal invasive tumor growth including lymph node metastasis in a genetic p53 knockout mouse model. Loss of p53 was associated with increased intestinal permeability causing formation of an NF-kB dependent inflammatory microenvironment and the induction of epithelial-mesenchymal transition regulated by NF-kB. p53 was shown to have a novel tissue specific tumor suppressive role as guardian of invasiveness apart from its well-established role in cell cycle regulation, apoptosis and senescence. After all NF-kB is substantially involved in cell type plasticity during tumor initiation and tumor invasion and is responsible for the recruitment of an inflammatory microenvironment. |
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