Nicotinamide N-methyltransferase induces the proliferation and invasion of squamous cell carcinoma cells

Cutaneous squamous cell carcinoma (cSCC) is a common malignancy initiated by keratinocytes of the epidermis, which are able to invade the dermis and its periphery. Although most patients with cSCC present with curable localized tumors, recurrence, metastasis and mortality occasionally occur. In the present study, nicotinamide N-methyltransferase (NNMT) was identified as an upregulated protein in the SCC12 cell line, which has high invasive potential compared with the SCC13 cell line. The effects of NNMT knockdown on proliferation, migration and invasion were investigated using SCC cells. shRNA-mediated downregulation of NNMT expression levels inhibited the proliferation and density-dependent growth of SCC12 cells. In addition, the results of a cell motility assay showed that the migration and invasion of SCC cells were markedly decreased in NNMT-knockdown cells. The assessment of epithelial-mesenchymal transition (EMT)-associated gene expression using PCR array analysis revealed that high NNMT expression levels were accompanied by high expression levels of EMT-associated genes, and that NNMT knockdown effectively suppressed the expression of matrix metalloproteinase 9, osteopontin, versican core protein and zinc finger protein SNAI2 in SCC12 cells. These results revealed that the upregulation of NNMT induced cellular invasion via EMT-related gene expression in SCC cells.