The arylamine N-acetyltransferases are a family of enzymes that catalyze the acetylation of many aromatic and heterocyclic amine compounds. In humans, there are two N-acetyltransferase isozymes, NAT1 and NAT2. Interest in the potential role of NAT1 in cancer began with the observation that this gene is often differentially expressed in subtypes of breast and prostate cancers. Indeed, NAT1 has been reported as one of the most robust biomarkers for luminal breast cancer. Further studies have established that over-expression of NAT1 can confer growth advantage and chemo-resistance in some cancer cells. In our laboratory, we have found that inhibition of NAT1 with either small molecule inhibitors or siRNA can lead to a marked phenotypic change in a number of different cancer cell types. For example, in the human colon cancer line HT-29, inhibition of NAT1 leads to the up-regulation of E-cadherin, contact inhibition, and reduced growth at confluence. We have also observed using invasive breast cancer cell lines that inhibition of NAT1 is associated with a change in cell shape, and decreased proliferation. Moreover, these cells lose cell surface filopodia and their ability to invade in vitro. In addition, nude mice injected intravenously with MDA-MB-231 NAT1 knock-down cells showed reduced lung tumour formation. As well as the changes in cell phenotype, growth and invasion, we have also observed a change in the metabolic capacity of cells where NAT1 has been knocked down with siRNA. In particular, cells can lose their ability to utilize MTA in the methionine salvage pathway, suggesting they become methionine dependent. We conclude that NAT1 is a novel drug target in the treatment of cancer and other proliferative diseases.