DUB-3 regulation of tumor associated inflammation and tumor growth

The tumor microenvironment includes blood vessels, immune cells, fibroblasts, and tumor cells. Inflammation in tumor microenvironment leads to the initiation, promotion, invasion, and metastasis of cancer. Inflammation stimuli such as TNF-α, IL-1β and TLR ligands are capable of activating the NF-κB controlled inflammatory signaling in cancer cells. The activations by these stimuli are modulated by various signaling molecules including those control ubiquitination and deubiquitination in the NF-κB signaling pathway. The DUB-3, has been identified as a deubiquitinating enzyme that belongs to cytokine inducible DUBs. In this study, we investigated the function of DUB-3 in control of inflammatory responses in different cancer cells. Expression of DUB-3 in these cancer cells regulated IL-1β, LPS, and Pam3Cys induced cytokine and chemokine productions and generated favorable conditions for tumor growth. DUB-3 promoted in vivo tumorigenesis and tumor growth. H&E staining of tumor sections revealed higher leukocyte infiltration in the tumors. The expression of genes associated with inflammation were investigated, and higher expression of inflammatory cytokines and chemokines were observed in tumors. Taken together, these observations suggest that DUB-3 regulates tumor growth by modulating inflammatory associated function.