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

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

  • Cell Signal. 2023 Jun 1;110739. doi: 10.1016/j.cellsig.2023.110739.
Hong Wang 1 Xin Xu 2 Yikun Wang 2 Xiangfei Xue 2 Wanxin Guo 2 Susu Guo 2 Shiyu Qiu 2 Jiangtao Cui 3 Yongxia Qiao 4
Affiliations

Affiliations

  • 1 School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
  • 2 Shanghai Institute of Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, 200030, China.
  • 3 Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, 200030, China.
  • 4 School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China. Electronic address: [email protected].
Abstract

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 ICAM1 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.

Keywords

Adhesion molecule; Cell adhesion; Cell migration; N-myristoylation; Protein modifications.

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