Association Between Activation of Atypical NF-kappa B1 p105 Signaling Pathway and Nuclear beta-Catenin Accumulation in Colorectal Carcinoma

作者：Lauscher Johannes C; Groene Joern; Dullat Sonja; Hotz Birgit; Ritz Joerg P; Steinhoff Ulrich; Buhr Heinz J; Visekruna Alexander^*

来源：Molecular Carcinogenesis, 2010, 49(2): 121-129.

DOI：10.1002/mc.20606

• NF-kappa B1 p105
• CRD-BP
• beta-TrCP1
• beta-catenin
• colorectal carcinoma

Recent studies have demonstrated that increased expression of coding region determinant-binding protein (CRD-BP) in response to beta-catenin signaling leads to the stabilization of beta-TrCP1, a substrate-specific component of SCF E3 ubiquitin ligase complex, resulting in an accelerated degradation of I kappa B alpha and activation of canonical nuclear factor-kappa B (NF-kappa B) pathway. Here, we show that the noncanonical NF-kappa B1 p105 pathway is constitutively activated in colorectal carcinoma specimens, being particularly associated with beta-catenin-mediated increased expression of CRD-BP and beta-TrCP1. In the carcinoma tissues exhibiting high levels of nuclear beta-catenin the phospho-p105 levels were increased and total p105 amounts were decreased in comparison to that of normal tissue indicating an activation of this NF-kappa B pathway. Knockdown of CRD-BP in colorectal cancer cell line SW620 resulted in significantly higher basal levels of both NF-kappa B inhibitory proteins, p105 and I kappa B alpha. Furthermore decreased NF-kappa B binding activity was observed in CRD-BP siRNA-transfected SW620 cells as compared with those transfected with control siRNA. Altogether, our findings suggest that activation of NF-kappa B1 p105 signaling in colorectal carcinoma might be attributed to beta-catenin-mediated induction of CRD-BP and beta-TrCP1.

• 出版日期2010-2
• 单位河北医科大学