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. Author manuscript; available in PMC: 2015 Jan 11.
Published in final edited form as: FEBS Lett. 2011 Aug 11;585(20):3174–3184. doi: 10.1016/j.febslet.2011.08.007

Figure 2. Tumor virus encoded oncoproteins can effectively modulate cancer metastasis by regulating Nm23-H1 associated activities.

Figure 2

Following infection, tumor viruses encoded oncoproteins (EBV EBNA3C and EBNA1; KSHV LANA and HPV E7) target multiple cellular pathways, including metastasis. The presence of different viral proteins (EBNA1, EBNA3C and LANA) results in change in sub-cellular localization of Nm23-H1 from cytoplasmic to predominantly nuclear. In nucleus they form a stable complex. Together with Nm23-H1, EBNA3C induces transcriptional up-regulation of several genes, inducing MMP-9, Cox-2 and α-V integrin. These activities further alter cellular invasiveness and angiogenesis. Coupled with Nm23-H1, EBNA3C also rescues Necdin-mediated downregulation of its downstream promoter (VEGF). Necdin can interact with Nm23-H1 that further modulates Nm23-H1 associated NDP kinase as well as protein kinase activities. HPV encoded E7 oncoprotein interacts with Nm23-H1 and blocks granzyme A induced apoptosis, thereby promoting cell invasiveness.