Joydeb Kumar Kundu^a, Young-Joon Surh^{b, c, d,*}

^a College of Pharmacy, Keimyung University, Daegu, South Korea

^b Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea

^c WCU Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Sciences, Seoul 151-742, South Korea

^d Cancer Research Institute, Seoul National University, Seoul 110-744, South Korea

^*Corresponding author.

Abstract

The role of inflammation in carcinogenesis has been extensively investigated and well documented. Many biochemical processes that are altered during chronic inflammation have been implicated in tumorigenesis. These include shifting cellular redox balance toward oxidative stress; induction of genomic instability; increased DNA damage; stimulation of cell proliferation, metastasis, and angiogenesis; deregulation of cellular epigenetic control of gene expression; and inappropriate epithelial-to-mesenchymal transition. A wide array of proinflammatory cytokines, prostaglandins, nitric oxide, and matricellular proteins are closely involved in premalignant and malignant conversion of cells in a background of chronic inflammation. Inappropriate transcription of genes encoding inflammatory mediators, survival factors, and angiogenic and metastatic proteins is the key molecular event in linking inflammation and cancer. Aberrant cell signaling pathways comprising various kinases and their downstream transcription factors have been identified as the major contributors in abnormal gene expression associated with inflammation-driven carcinogenesis. The posttranscriptional regulation of gene expression by microRNAs also provides the molecular basis for linking inflammation to cancer. This review highlights the multifaceted role of inflammation in carcinogenesis in the context of altered cellular redox signaling.