头颈部鳞状细胞癌
蛋氨酸
癌症研究
生物
细胞周期
转移
细胞
癌症
生物化学
头颈部癌
氨基酸
遗传学
作者
Jiayi Li,Ruijie Wang,Mingyu Li,Zhiyuan Zhang,Shufang Jin,Hailong Ma
出处
期刊:Cancer Letters
[Elsevier]
日期:2024-02-27
卷期号:588: 216756-216756
被引量:2
标识
DOI:10.1016/j.canlet.2024.216756
摘要
The Yes-associated protein (YAP) plays a vital role in tumor progression and metabolic regulation. However, the involvement of YAP in metabolic reprogramming of head and neck squamous cell carcinoma remains unclear. Using RNA sequencing and ultra-high-performance liquid chromatography-tandem mass spectrometry, we observed that YAP increased the levels of the main metabolites and enzymes involved in methionine metabolism. APIP, an enzyme involved in the methionine salvage pathway, was transcriptionally activated by YAP. Further experiments showed that APIP promotes HNSCC cells migration and invasion in vitro and tumor metastasis in adjacent lymph nodes and distant organs in vivo. APIP also increases the levels of metabolites in the methionine cycle. We further found that methionine reversed the inhibition of HNSCC migration and invasion by APIP knockdown. In vivo experiments demonstrated that methionine addition promoted tumor metastasis. Mechanistically, the methionine cycle phosphorylated and inactivated GSK3β, then induced the epithelial mesenchymal transition pathway. Increased APIP expression was detected in patients with HNSCC, especially in tumors with lymph node metastasis. Metabolites of methionine cycle were also elevated in HNSCC patients. Our findings revealed that APIP, a novel target of YAP, promotes the methionine cycle and HNSCC metastasis through GSK3β phosphorylation.
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