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Published on: August 27, 2013
N-myristoyltransferase 1-mediated Src Myristoylation Promotes Non-receptor Tyrosine Kinase Pathways in Oral Squamous
Takuma Komiyama1, Goro Sugiyama2, Hanae Kamohara1
1Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
Background Aim:
N-myristoyltransferase 1 (NMT1), which myristoylates Src, is highly expressed in oral squamous cell carcinoma (OSCC). Although targeted therapies against epidermal growth factor receptor exist, their use is limited by resistance and toxicity, and NMT1-Src interactions remain unexplored. Herein, we aimed to evaluate the role of NMT1-mediated Src myristoylation in the malignant potential of OSCC.
Materials And Methods:
Myristoylation and the expression of NMT1 in OSCC were assessed using click chemistry and immunocytochemistry. RNA-seq and enrichment analyses were performed to compare OSCC cells with or without NMT1-siRNA treatment. Src activity was determined by measuring Src phosphorylation via western blotting. Expression and binding of NMT1 and Src were analyzed via immunoprecipitation using specific antibodies. HSC-2, HSC-3, WK2, and WK3F derived from human OSCC in vitro were also used to confirm malignancy by siRNA of siNMT1 in OSCC cell lines.
Results:
NMT1 and Src expression was detected in all OSCC cell lines. RNA-seq analysis of SAS cells transfected with NMT1-siRNA revealed decreased expression of genes related to cell adhesion and angiogenesis. WK3F cells, which exhibit high malignancy, showed markedly higher NMT1 expression than other cell lines. Immunocytochemistry showed that Src membrane localization was reduced in all of the OSCC cell lines with NMT1 knockdown. Co-immunoprecipitation analysis confirmed that NMT1 was bound to Src during myristoylation.
Conclusion:
NMT1 promotes OSCC malignancy by mediating Src myristoylation.
Insights
N-myristoyltransferase 1 (NMT1) promotes oral squamous cell carcinoma (OSCC) malignancy. NMT1 mediates Src myristoylation, a key interaction driving OSCC progression and potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- N-myristoyltransferase 1 (NMT1) is highly expressed in oral squamous cell carcinoma (OSCC).
- Existing targeted therapies for OSCC have limitations, and the role of NMT1-Src interactions is unexplored.
- NMT1 mediates the myristoylation of Src, a critical signaling protein.
Purpose of the Study:
- To investigate the role of NMT1-mediated Src myristoylation in OSCC malignancy.
- To explore NMT1 as a potential therapeutic target in OSCC.
Main Methods:
- Assessed NMT1 expression and myristoylation using click chemistry and immunocytochemistry.
- Utilized RNA-sequencing and western blotting to analyze gene expression and Src activity.
- Employed co-immunoprecipitation to confirm NMT1-Src binding and siRNA to knockdown NMT1 in OSCC cell lines.
Main Results:
- NMT1 and Src were expressed in all tested OSCC cell lines.
- NMT1 knockdown reduced expression of genes involved in cell adhesion and angiogenesis.
- NMT1 binds to Src during myristoylation, and NMT1 knockdown decreased Src membrane localization.
Conclusions:
- NMT1 promotes OSCC malignancy through its mediation of Src myristoylation.
- NMT1-Src myristoylation represents a potential therapeutic avenue for OSCC.
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