Nmt1-KO Mouse

Nmt1, short for N-myristoyltransferase 1, is an essential eukaryotic enzyme. It catalyzes the transfer of myristoyl groups to the amino-terminal residues of numerous proteins. This process is crucial for the growth and development of many eukaryotes and viruses. N-myristoylation, the reaction it mediates, is involved in various cellular processes such as signal transduction, cellular transformation, and tumorigenesis [4].

In cancer research, multiple studies have demonstrated the significance of Nmt1. In hepatocellular carcinoma (HCC), upregulation of Nmt1 expression enhanced tumor growth, while Nmt1 knockdown suppressed it both in vitro and in vivo. Nmt1 was found to myristoylate VILIP3 protein, and high Nmt1 or VILIP3 expression was associated with advanced stages and poor survival in HCC. Desloratadine, an anti-allergic drug, binds to Nmt1 and inhibits its enzymatic activity, disrupting the Nmt1-mediated myristoylation of VILIP3 protein and subsequent NFκB/Bcl-2 signaling [1]. In breast cancer, genetic inhibition of Nmt1 suppressed the initiation, proliferation, and invasion of breast cancer cells in vitro and in vivo. Nmt1 knockdown promoted oxidative stress, which along with endoplasmic reticulum (ER) stress, activated the JNK pathway leading to autophagy and abrogating breast cancer progression, especially in triple-negative breast cancer (TNBC) [3]. In non-small cell lung cancer (NSCLC), Nmt1 was highly expressed in spheroid cells and facilitated the stemness of NSCLC cells by activating the PI3K/AKT pathway. It also accelerated NSCLC tumor metastasis and resistance to cisplatin [2]. In liver cancer, Nmt1-mediated N-myristoylation differentially regulated the ubiquitination of target proteins. It suppressed anti-tumorigenic proteins and stimulated pro-tumorigenic proteins, resulting in a pro-tumorigenic outcome [5].

In conclusion, Nmt1 is crucial for the N-myristoylation of proteins, which is involved in multiple biological processes. Through gene knockout or knockdown models in various cancer types, Nmt1 has been shown to play significant roles in tumor development, metastasis, and drug resistance. These findings suggest that Nmt1 could be a potential biomarker and therapeutic target for treating cancers such as HCC, breast cancer, NSCLC, and liver cancer.

References:

1. Tan, Xiang-Peng, He, Yan, Yang, Jing, Guan, Xin-Yuan, Li, Bin. 2023. Blockade of NMT1 enzymatic activity inhibits N-myristoylation of VILIP3 protein and suppresses liver cancer progression. In Signal transduction and targeted therapy, 8, 14. doi:10.1038/s41392-022-01248-9. https://pubmed.ncbi.nlm.nih.gov/36617552/

2. Zou, Wailong, Zhang, Xinjun, Wang, Yumin, Zhang, Jia, Chen, Jichao. 2022. NMT1 Enhances the Stemness of NSCLC Cells by Activating the PI3K/AKT Pathway. In Pharmacology, 107, 486-494. doi:10.1159/000525095. https://pubmed.ncbi.nlm.nih.gov/35732157/

3. Deng, Lu, Gao, Xinlei, Liu, Bingjie, Wu, Qingfa, Liu, Suling. 2018. NMT1 inhibition modulates breast cancer progression through stress-triggered JNK pathway. In Cell death & disease, 9, 1143. doi:10.1038/s41419-018-1201-x. https://pubmed.ncbi.nlm.nih.gov/30446635/

4. Wang, Hong, Xu, Xin, Wang, Jiayi, Qiao, Yongxia. . The role of N-myristoyltransferase 1 in tumour development. In Annals of medicine, 55, 1422-1430. doi:10.1080/07853890.2023.2193425. https://pubmed.ncbi.nlm.nih.gov/37140999/

5. Zhu, Guoqing, Wang, Feng, Li, Haojie, Qiao, Yongxia, Pan, Qiuhui. 2021. N-Myristoylation by NMT1 Is POTEE-Dependent to Stimulate Liver Tumorigenesis via Differentially Regulating Ubiquitination of Targets. In Frontiers in oncology, 11, 681366. doi:10.3389/fonc.2021.681366. https://pubmed.ncbi.nlm.nih.gov/34136404/