Multi-omics revealed GOT1/ALDH3A1 pathway attenuated head and neck squamous cell carcinoma and increased cisplatin...

Area of Science:

• Oncology
• Biochemistry
• Molecular Biology

Background:

• Head and neck squamous cell carcinoma (HNSCC) has limited treatment options.
• The role of aspartate aminotransaminase (GOT1) in HNSCC pathogenesis is not well understood.
• GOT1 is implicated in cancer development, necessitating investigation in HNSCC.

Purpose of the Study:

• To investigate the role of GOT1 in HNSCC.
• To determine the effects of GOT1 inhibition on HNSCC cell behavior and tumor growth.
• To explore the underlying mechanisms of GOT1's action in HNSCC.

Main Methods:

• Proteomics and metabolomics were used to identify GOT1 expression in HNSCC tissues.
• Functional assays (CCK8, wound healing, colony formation, EdU, TUNEL, flow cytometry) assessed proliferation and apoptosis after GOT1 knockdown.
• Mitochondrial function, reactive oxygen species (ROS) levels, and gene expression (JC-1, qRT-PCR, RNA-seq) were analyzed.

Main Results:

• High GOT1 expression was identified in human HNSCC tissues.
• GOT1 knockdown significantly inhibited HNSCC cell proliferation and promoted apoptosis.
• GOT1 inhibition led to mitochondrial dysfunction, increased ROS production, and enhanced sensitivity to cisplatin, reducing tumor volume in vivo.

Conclusions:

• GOT1 knockdown suppresses HNSCC progression by inducing mitochondrial dysfunction and ROS overproduction.
• This mechanism enhances cancer cell apoptosis and increases sensitivity to cisplatin chemotherapy.
• GOT1 inhibition represents a potential therapeutic strategy for improving clinical outcomes in HNSCC.