NMT1 sustains ICAM-1 to modulate adhesion and migration of tumor cells.

Protein modifications have significant effects on tumorigenesis. N-Myristoylation is one of the most important lipidation modifications, and N-myristoyltransferase 1 (NMT1) is the main enzyme required for this process. However, the mechanism underlying how NMT1 modulates tumorigenesis remains largely unclear. Here, we found that NMT1 sustains cell adhesion and suppresses tumor cell migration. Intracellular adhesion molecule 1 (ICAM-1) was a potential functional downstream effector of NMT1, and its N-terminus could be N-myristoylated. NMT1 prevented ubiquitination and proteasome degradation of ICAM-1 by inhibiting Ub E3 ligase F-box protein 4, which prolonged the half-life of ICAM-1 protein. Correlations between NMT1 and ICAM-1 were observed in liver and lung cancers, which were associated with metastasis and overall survival. Therefore, carefully designed strategies focusing on NMT1 and its downstream effectors might be helpful to treat tumors.