BCAT1 overexpression regulates proliferation and c-Myc/GLUT1 signaling in head and neck squamous cell carcinoma

Abstract

Branched chain amino acid transaminase 1 (BCAT1) overexpression has been reported in various cancers; however, at present, its significance and biological role in head and neck squamous cell carcinoma (HNSCC) remain unknown. BCAT1 protein expression was upregulated in 56/106 (52.8%) cases of HNSCC. BCAT1 overexpression was associated with tumor-node-metastasis stage, tumor stage and nodal metastasis. The Cancer Genome Atlas data suggested that high BCAT1 expression was associated with poor patient survival. Oncomine data suggested that BCAT1 expression was increased in HNSCC. Functionally, BCAT1 overexpres- sion promoted cell proliferation, colony formation, invasion and cisplatin resistance in FaDu cells. BCAT1 overexpression also upregulated the mitochondrial membrane potential, and increased ATP production, glucose consumption and glucose uptake. Western blotting demonstrated that BCAT1 overexpression upregulated c-Myc and glucose transporter 1 (GLUT1) protein levels. Depletion of c-Myc using small inter- fering RNA abolished the influence of BCAT1 on GLUT1. Chromatin immunoprecipitation assays demonstrated that c-Myc has binding sites in the GLUT1 promoter. Collectively, the present findings suggested that BCAT1 is upregulated in human HNSCC and regulates HNSCC cell proliferation, invasion, cisplatin sensitivity and c-Myc/GLUT1 signaling.