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在PTEN-null前列腺中,PLEKHS1驱动PI3Ks并重塑途径平衡

Tamara A M Chessa¹, Piotr Jung¹, Arqum Anwar¹

¹Signalling Programme, Babraham Institute, Cambridge CB22 3AT, UK.

|August 11, 2023

概括

在PTEN-null前列腺癌中,PLEKHS1适配蛋白通过逃避反和促进AKT酸化来驱动过度活跃的PIP3/PI3K信号,从而支持瘤生长.

科学领域:

分子生物学分子生物学
癌症生物学癌症生物学
细胞信号传递细胞信号传递

背景情况:

酸3-酶 (PI3K) 网络调节新陈代谢,在癌症中经常过度激活,通常是由于PTEN酸酶的损失.
了解正常组织中PI3K网络的驱动因素及其适应过度激活对于癌症研究至关重要.

研究的目的:

调查驱动PI3K活动的信号网络在健康和PTEN-null小鼠前列腺中.
为了确定关键的分子参与者和机制,负责持续PI3K通路激活在没有PTEN的情况下.

主要方法:

在小鼠前列腺模型中分析PI3K网络信号.
蛋白质-蛋白质相互作用和翻译后修改的识别和表征.
在人类前列腺癌样本中对分子标记物与PI3K通路活性进行相关性分析.

主要成果:

在健康的小鼠前列腺中,PI3K活性通过RTK/IRS信号和反抑制来调节.
在PTEN-null前列腺中,适应蛋白PLEKHS1成为PI3K网络的主导激活剂.
通过逃避反,PLEKHS1维持了PIP3水平和AKT酸化,并通过PI3K和Src家族激酶驱动的YXXM基因进行增强酸化.

结论:

在PTEN缺陷前列腺癌中,PLEKHS1充当PI3K通路激活的关键调解者.
对PLEKHS1的受体独立,Src依赖酸化会产生一个积极的反循环,推动瘤的进展.
PLEKHS1和Src激活是人类前列腺癌中具有PI3K通路激活的潜在生物标志物和治疗标.

关键词:

美国国税局1 IRS1 在PI3K中,PI3K是指PI3K.这就是Plekhs1的意思.在这里,我们可以使用PTEN.这是一种Src-家族的激酶.前列腺前列腺前列腺

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