Department of Otolaryngology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
Oncol Rep. 2021 May;45(5). doi: 10.3892/or.2021.8003. Epub 2021 Mar 24.
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 overexpression 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 interfering 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.
支链氨基酸转氨酶 1（BCAT1）的表达在各种癌症中均有报道；然而，目前其在头颈部鳞状细胞癌（HNSCC）中的意义和生物学作用尚不清楚。BCAT1 蛋白在 106 例 HNSCC 病例中的 56 例（52.8%）中呈上调表达。BCAT1 过表达与肿瘤-淋巴结-转移分期、肿瘤分期和淋巴结转移相关。癌症基因组图谱数据表明，BCAT1 高表达与患者生存不良相关。Oncomine 数据表明，BCAT1 在 HNSCC 中表达增加。功能上，BCAT1 过表达促进 FaDu 细胞的增殖、集落形成、侵袭和顺铂耐药性。BCAT1 过表达还上调了线粒体膜电位，并增加了 ATP 产生、葡萄糖消耗和葡萄糖摄取。Western blot 分析表明，BCAT1 过表达上调了 c-Myc 和葡萄糖转运蛋白 1（GLUT1）蛋白水平。使用小干扰 RNA 耗尽 c-Myc 可消除 BCAT1 对 GLUT1 的影响。染色质免疫沉淀试验表明，c-Myc 在 GLUT1 启动子上具有结合位点。综上所述，本研究结果表明，BCAT1 在人 HNSCC 中上调，并调节 HNSCC 细胞的增殖、侵袭、顺铂敏感性和 c-Myc/GLUT1 信号通路。
