Qiang Du, MD
Research Assistant Professor of Surgery
MD, Harbin Medical University, Harbin, China
iNOS/NO, Wnt signaling and cancer
The Wnt/beta-catenin pathway and inflammation play important roles in carcinogenesis, but the molecular mechanism is still to be elucidated. My research interest focuses on human inducible nitric oxide (NO) synthase (hiNOS) as a target of Wnt/beta-catenin signaling and the role of NF-kappaB in the interaction of Wnt/beta-catenin and hiNOS/NO pathways in cancer cells. NO, an important mediator of inflammation, and beta-catenin, a component of the Wnt-adenomatous polyposis coli signaling pathway, contribute to the development of cancer. We first found that beta-catenin up-regulates hiNOS and increases NO production, which suggests a novel mechanism by which the Wnt/beta-catenin signaling pathway may contribute to cancer. Furthermore, since the hiNOS gene is also regulated by nuclear factor kappaB (NF-kappaB), we tested the hypothesis that Wnt/beta-catenin signaling regulates cytokine- or tumor necrosis factor alpha (TNFalpha)-induced hiNOS expression through interaction with NF-kappaB. Our in vitro and in vivo data show that beta-catenin signaling inversely correlates with cytokine-induced hiNOS and other NF-kappaB-dependent gene expression. These findings underscore the complex role of Wnt/beta-catenin, NF-kappaB, and iNOS signaling in the pathophysiology of inflammation-associated carcinogenesis. hiNOS/NO appears to be a critical regulator for development of cancer, whose signaling mechanisms through Wnt/beta-catenin and NF-kappaB will be studied in my long-term research.