通过通过AKT1/mTOR通路调节HK2来调节SPI1参与恶性黑色素瘤的发生
Chunlei Liu1, Xiujuan Qiu2, Jun Gao3
1Department of dermatology, Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang, China.
Journal of cellular and molecular medicine
|August 4, 2023
概括
原型瘤基因Spi-1 (SPI1) 通过增加葡萄糖分解和转移来驱动黑色素瘤的进展. 向SPI1抑制癌细胞生长,并影响AKT1/mTOR通路,提供一种潜在的治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 斯皮-1原瘤基因 (SPI1) 与癌症发生有关.
- 了解SPI1在黑色素瘤中的作用对于开发向疗法至关重要.
研究的目的:
- 为了研究SPI1在黑色素瘤中的调节机制.
- 确定SPI1对黑色素瘤细胞活力,转移和糖解的影响.
- 为了阐明SPI1,hexokinase 2 (HK2) 和AKT1/mTOR通路之间的关系.
主要方法:
- 定量实时PCR (qRT-PCR) 和西式涂抹用于基因和蛋白质表达.
- 细胞活性的CCK-8测定.
- 双露西法酶记者测定和ChIP用于目标验证.
- 对细胞迁移的伤口愈合试验.
- 测量葡萄糖溶解标记 (葡萄糖消耗,乳酸生产,ATP水平).
- 黑色素瘤组织中SPI1和HK2的免疫组织化学.
主要成果:
- 与正常对照人群相比,黑色素瘤细胞和组织中的SPI1表达显著增加.
- 降低SPI1降低了黑色素瘤细胞活力,转移和糖解.
- SPI1直接准并抑制2基酶 (HK2) 的表达.
- 过度表达HK2部分逆转了SPI1敲击的抑制作用.
- 通过AKT1/mTOR通路抑制了黑色素瘤的进展.
结论:
- SPI1通过增强糖解和转移来促进黑色素瘤的进展.
- SPI1直接调节HK2的表达,有助于代谢重编程.
- 在黑色素瘤的发展中,SPI1/HK2轴和AKT1/mTOR通路至关重要.
- 准SPI1为黑色素瘤提供了潜在的治疗策略.
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