Figure 1. Overview of the role of epigenetic disruption of cell signaling regulators mediated by EBV infection during NPC tumorigenesis. DAB2, disabled-2; DLC1, deleted in liver cancer 1; DNMT, DNA methyltransferase; EBV, Epstein-Barr virus; HIN1, high-in-normal 1; LMP1, latent membrane protein 1; LMP2A, latent membrane protein 2A; NPC, nasopharyngeal carcinoma; PcG, Polycomb protein; RASAL1, Ras GAP-activating-like protein 1; RASSF1A, Ras association domain family 1A; TSG, tumor suppressor gene; UCHL1, Ubiquitin carboxyl-terminal hydrolase L1; WIF1, Wnt inhibitory factor-1. Ras GTPase signaling negative regulators (e.g., RASAL1, RASSF1A, HIN1, and DAB2), Rho GTPase signaling negative regulators (e.g., DLC1), p53 signaling positive regulators (e.g., UCHL1 and TP73), Wnt/β-catenin signaling negative regulators (e.g., WIF1), cell cycle control-DNA damage signaling regulators, cell adhesion regulators, and apoptosis regulators play important roles in the initiation and progression of NPC. Epigenetic silencing of these antagonists or activators through promoter CpG methylation or histone modifications, initiated or mediated by EBV-encoded viral proteins, disrupts multiple cell signaling pathways during NPC tumorigenesis.