Anti-apoptotic N-cadherin signaling and its prognostic implication in human hepatocellular carcinomas
Affiliations: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
- Published online on: May 1, 2006 https://doi.org/10.3892/or.15.5.1117
- Pages: 1117-1123
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...
This article is mentioned in:
N-cadherin signaling has recently been implicated in the progression of certain epithelial tumors by promoting invasion and dissemination of cancer cells. N-cadherin has also been reported to exert an anti-apoptotic effect. In this study, we attempted to evaluate the participation of this adhesion molecule in the progression of human hepatocellular carcinomas (HCCs) by analyzing its anti-apoptotic signaling as well as its prognostic implication in HCC patients. N-cadherin was found to be expressed in human HCCs. We established a stable human HCC cell line expressing a truncated N-cadherin, NCadΔC, with a dominant-negative action. NCadΔC-expressing cells were more susceptible to bile acid-induced apoptosis than control cells. N-cadherin was found to complex with procaspase-8, and this association was diminished in NCadΔC-expressing cells, leading to enhanced procaspase-8 recruitment to death-inducing signaling complex following bile acid treatment. A clinicopathological analysis in patients who had undergone surgical resection for HCC revealed that tumoral N-cadherin up-regulation was significantly related to poor recurrence-free and overall survival. Our findings implicate N-cadherin signaling as contributing to HCC progression by exerting anti-apoptotic effects. Thus, we suggest that the selective interruption of this signaling may have therapeutic potential.