N-myristoyltransferase-1 deficiency blocks myristoylation of LAMTOR1 and inhibits bladder cancer progression

Abstract

N-myristoyltransferase-1 (NMT1) catalyzes protein posttranslational myristoylation and functions as an oncogene in various cancers, although its roles in bladder cancer remain elusive. Here, we demonstrated that NMT1 was obviously upregulated in bladder cancer and correlated with overall survival and poor prognosis. Elevation of NMT1 promotes cancer progression and inhibits autophagy in vitro and in vivo. Furthermore, we confirm that LAMTOR1 was myristoylated by NMT1 at Gly 2, resulting in increased LAMTOR1 protein stability and lysosomal localization. Importantly, B13, an inhibitor of NMT1 enzymatic activity, exerted its anti-tumor effects against bladder cancer cells in vitro and in vivo. Taken together, these findings uncover a molecular mechanism of NMT1 in modulating bladder cancer progression and indicate that targeting NMT1 may represent a novel clinical intervention in bladder cancer.

Keywords: Autophagy; B13; Bladder cancer; LAMTOR1; Myristoylation; NMT1.