期刊
CANCER LETTERS
卷 529, 期 -, 页码 126-138出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2022.01.001
关键词
Autophagy; B13; Bladder cancer; LAMTOR1; Myristoylation; NMT1
类别
The study reveals that NMT1 is upregulated in bladder cancer and is associated with poor prognosis. Elevated NMT1 promotes cancer progression and inhibits autophagy. Additionally, NMT1 myristoylates LAMTOR1, leading to increased protein stability and lysosomal localization. The NMT1 inhibitor B13 demonstrates anti-tumor effects against bladder cancer cells.
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.
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