在肝细胞癌中,BTF3通过调节GLUT1来促进肝细胞癌的增殖和糖解
Peng Wang1, Jianmin Sun1, Chengming Sun1
1Department of Hepatobiliary and Pancreatic Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China.
Cancer biology & therapy
|June 29, 2023
概括
基本转录因子3 (BTF3) 通过调高分叉盒M1 (FOXM1) 和葡萄糖输送器1 (GLUT1) 的调节,促进肝细胞癌 (HCC) 的生长和糖解. 抑制BTF3可以减少HCC模型中的瘤进展.
科学领域:
- 分子瘤学分子瘤学
- 癌症新陈代谢 癌症新陈代谢
背景情况:
- 全球肝细胞癌 (HCC) 发病率正在上升,需要对其潜在机制进行研究.
- 异常糖解是癌症的标志,但HCC中的调节途径需要进一步阐明.
- 基本转录因子3 (BTF3) 与癌症有关,但其在HCC糖解中的具体作用尚不清楚.
研究的目的:
- 研究BTF3在促进肝细胞癌 (HCC) 扩散和糖解中的作用.
- 阐明BTF3影响HCC的分子机制,重点关注FOXM1/GLUT1轴.
- 评估在HCC中准BTF3的治疗潜力.
主要方法:
- 使用在线数据库,RT-qPCR和西方 blot.使用BTF3,FOXM1和GLUT1的表达式分析.
- 通过CCK-8,EDU结合,海马XF分析仪和代谢物测定评估HCC细胞增殖和糖解.
- 使用双露西法酶记者和共免疫沉测定验证BTF3-FOXM1相互作用;使用异种移植小鼠模型进行体内研究.
主要成果:
- 在HCC组织和细胞中,BTF3的表达显著升高.
- BTF3的淘汰抑制了HCC细胞的活力,增殖和糖解 (ECAR,葡萄糖消耗,乳酸盐生产).
- BTF3直接与FOXM1相互作用,对FOXM1和GLUT1的表达进行上调,从而增强糖解和增殖; BTF3的抑制在体内减少瘤生长.
结论:
- 通过FOXM1/GLUT1信号轴,BTF3在促进HCC细胞增殖和糖解方面发挥着至关重要的作用.
- 向BTF3代表了肝细胞癌的潜在治疗策略.
- BTF3-FOXM1-GLUT1通路是HCC中代谢重编程的关键驱动因素.
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