在细胞癌中TFE3/PI3K/Akt/mTOR轴影响瘤微环境
Chungsu Hwang1, Yun Kyung Kang1, Ji Yun Kim1
1Department of Pathology, Pusan National University Yangsan Hospital, Yangsan, Korea.
The American journal of pathology
|April 8, 2024
概括
转录因子E3 (TFE3) 对细胞癌 (RCC) 中的酸丁3-酶 (PI3K) /Akt通路产生影响. 调节TFE3会影响Akt活性,这表明PI3K/Akt抑制剂可以通过影响瘤微环境来治疗RCC.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 细胞信号传递 细胞信号传递
背景情况:
- 酸丁3-酶 (PI3K) /Akt通路对于细胞癌 (RCC) 的进展,转移和治疗耐药性至关重要.
- 转录因子E3 (TFE3) 表达与预后不佳相关,并影响RCC患者的瘤微环境.
研究的目的:
- 研究TFE3表达与细胞癌中的PI3K/Akt通路之间的关系.
- 阐明TFE3在调节PI3K/Akt信号级联中的关键组件中的作用.
主要方法:
- 利用siRNA和shRNA用于TFE3下调和pcDNA3.1用于UOK146RCC细胞中TFE3过度表达.
- 用于PI3K和哺乳动物目标的拉帕素 (mTOR) 抑制剂.
- 采用西式涂抹来量化TFE3,编程死亡连接物1,酸-Akt和Akt水平.
主要成果:
- 降低TFE3的调节导致酸-Akt表达的显著增加.
- 过度表达TFE3导致-Akt表达显著下降.
- 用PI3K抑制剂 (LY294002) 治疗增加了TFE3的表达,并降低了酸-Akt水平.
结论:
- 在细胞癌的背景下,TFE3在调节PI3K/Akt通路方面发挥着重要作用.
- 用抑制剂向PI3K/Akt通路可能是RCC的可行的治疗策略,可能通过改变瘤微环境.
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