这三种AKT异型均可在人类肝细胞癌细胞系中抑制氧化代谢和乳酸生产
Ling-Yu Tian1,2, Daniel J Smit1, Nadezhda V Popova1
1Institute of Biochemistry and Signal Transduction, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany.
每个AKT异型 (AKT1,AKT2,AKT3) 独立地促进肝细胞癌 (HCC) 细胞代谢,通过调节酸盐脱酶来增加氧气消耗和乳酸盐生产.
科学领域:
- * 瘤学 瘤学是一门专业.
- * 分子生物学 * 分子生物学
- * 癌症代谢 * 癌症代谢
背景情况:
- *肝细胞癌 (HCC) 是一种主要的肝癌亚型,与病毒性肝炎,酒精和NAFLD有关.
- *构成PI3K/AKT通路的激活在HCC中很常见,导致瘤的进展.
- *AKT异型 (AKT1,AKT2,AKT3) 调节细胞代谢,但它们在HCC中的具体作用尚不清楚.
研究的目的:
- * 调查AKT1,AKT2和AKT3在调节HCC细胞代谢中的不同作用.
- *阐明 AKT 异型对 HCC 细胞代谢活动的影响机制.
主要方法:
- *在人类HCC细胞系 (Hep3B,Huh7) 中,AKT异型 (AKT1,AKT2,AKT3) 的过度表达和抑制.
- *测量氧气消耗率 (OCR),细胞外酸化率 (ECAR),ATP生产和乳酸盐生产.
- * 酸盐脱酶 (PDH) 酸化在Ser232.2的分析.
主要成果:
- *激活AKT1,AKT2或AKT3的过度表达增加了OCR,ATP生产,最大呼吸和备用呼吸能力.
- * 任何AKT异型的抑制降低了HCC细胞中的OCR,ECAR和乳酸盐生产.
- *在AKT异形敲除后OCR降低与Ser232的PDH酸化增加相关,抑制呼吸.
结论:
- *所有三种AKT异型 (AKT1,AKT2,AKT3) 独立地增强了HCC中的线粒体呼吸和糖解.
- *AKT异型通过调节酸盐脱酶活性来调节HCC代谢.
- * 向AKT异型可能为改变HCC细胞代谢提供治疗策略.
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