Effects of human arylamine N ‐acetyltransferase I knockdown in triple‐negative breast cancer cell lines

Expression of human arylamine N ‐acetyltransferase I ( NAT 1) has been associated with various cancer subtypes and inhibition of this enzyme with small molecule inhibitors or si RNA affects cell growth and survival. Here, we have investigated the role of NAT 1 in the invasiveness of breast cancer cells both in vitro and in vivo. We knocked down NAT 1 using a lentivirus‐based sh RNA approach and observed marked changes in cell morphology in the triple‐negative breast cancer cell lines MDA ‐ MB ‐231, MDA ‐ MB ‐436, and BT ‐549. Most notable was a reduction in the number and size of the filopodia protrusions on the surface of the cells. The loss of filopodia could be rescued by the reintroduction of NAT 1 into the knockdown cells. NAT 1 expression was localized to the lamellipodia and extended into the filopodia protrusions. In vitro invasion through Geltrex was significantly inhibited in both the MDA cell lines but not in the BT ‐549 cells. The expression of Snail increased when NAT 1 was knocked down, while other genes associated with mesenchymal to epithelial transition (vimentin, cytokeratin‐18, and Twist) did not show any changes. By contrast, both N‐cadherin and β ‐catenin were significantly reduced. When MDA ‐ MB ‐231 cells expressing sh RNA were injected in vivo into BALB /c nu/nu nude mice, a significant reduction in the number of colonies that formed in the lungs was observed. Taken together, the results show that NAT 1 can alter the invasion and metastatic properties of some triple‐negative breast cancer cells but not all. The study suggests that NAT 1 may be a novel therapeutic target in a subset of breast cancers.