OGG1 as an Epigenetic Reader Affects NFB: What This Means for Cancer

OGG1-enabled NF kappa B activity can promote cancer progression via a number of key mechanisms that include phenotypic transitions of cancer and stromal cells, expression and secretion of molecules that modulate innate immunity, and alteration of the vascular network. Under oxidative stress, the supraphysiological levels of nongenotoxic 8-oxoGua, along with redox inactivation of OGG1 via cysteine oxidation and potential dimerization, provide multiple interfaces with redoxactivated/modulated NF kappa B and other transacting factors, including Myc. This promotes not only cell proliferation, the expression of innate immune genes, and angiogenesis but also the metastatic capability of cells involving the expression of epithelial-mesenchymal transition genes. Mounting evidence supports the idea that increased levels of oxidative stress play a crucial role in the onset and progression of solid and lymphoid malignancies. This is achieved by gaining mutations and by activating signaling pathways that promote cell survival, cell proliferation, and resistance to treatment modalities. 8-oxoguanine glycosylase 1 (OGG1), which was initially identified as the enzyme that catalyzes the first step in the DNA base excision repair pathway, is now also recognized as a modulator of gene expression. What is important for cancer is that OGG1 acts as a modulator of NF kappa B-driven gene expression. Specifically, oxidant stress in the cell transiently halts enzymatic activity of substrate-bound OGG1. The stalled OGG1 facilitates DNA binding of transactivators, such as NF kappa B to their cognate sites, enabling the expression of cytokines and chemokines, with ensuing recruitment of inflammatory cells. Recently, we highlighted chief aspects of OGG1 involvement in regulation of gene expression, which hold significance in lung cancer development. However, OGG1 has also been implicated in the molecular underpinning of acute myeloid leukemia. This review analyzes and discusses how these cells adapt through redox-modulated intricate connections, via interaction of OGG1 with NF kappa B, which provides malignant cells with alternative molecular pathways to transform their microenvironment, enabling adjustment, promoting cell proliferation, metastasis, and evading killing by therapeutic agents.