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LKB1和STRADα促进了上皮卵巢癌球状细胞入侵

Charles B Trelford^1,2, Adrian Buensuceso^1,2, Emily Tomas^1,2

¹The Mary & John Knight Translational Ovarian Cancer Research Unit, Verspeeten Family Cancer Centre, London, ON N6A 4L6, Canada.

|November 27, 2024

概括

肝激酶B1 (LKB1) 和STRAD信号传导通过增强矩阵金属蛋白酶 (MMP) 活性和纤维内素表达来促进上皮卵巢癌 (EOC) 转移,这表明LKB1通路抑制剂作为治疗策略.

科学领域:

在瘤学瘤学.
细胞生物学细胞生物学
分子生物学分子生物学

背景情况:

晚期上皮卵巢癌 (EOC) 具有广泛的腹膜传播的特征,通常涉及.
EOC转移取决于称为球状体的多细胞聚合物的形成.
肝激酶B1 (LKB1) 对于EOC球体活力至关重要,其损失在临床前模型中降低了瘤负担.

研究的目的:

研究LKB1复合体在控制人类EOC球体的入侵性质中的作用.
确定LKB1及其激活剂STRAD如何影响EOC细胞入侵和转移.

主要方法:

使用CRISPR/Cas9对LKB1的淘汰和针对STRAD的RNAi来对抗LKB1的信号传输.
使用Matrigel进行实时入侵监测,进行Transwell测试,球状体重新连接和中层清除测试.
采用体图和3D有机体模型来评估矩阵金属蛋白酶 (MMP) 活性和整体有机体生长.

主要成果:

失去LKB1和STRAD信号,显著减少了EOC通过Matrigel和Transwell膜的球状体入侵.
在没有LKB1和STRAD的情况下,中皮细胞清除率降低.
损失LKB1降低了MMP活性,而纤维内素恢复了球体的侵入性; 3D器官区域也减少了.

结论:

对于EOC转移来说,LKB1和STRAD信号传递至关重要,通过MMP活性和纤维菌素表达促进入侵.
准LKB1通路,包括LKB1和STRAD,是抑制EOC传播的潜在治疗策略.

关键词:

与STE20相关的酶适应蛋白 (STRAD)卵巢上皮癌 (EOC) 是一种肝激酶B1 (LKB1) 是一种肝激酶.介质细胞的清除率.转移转移转移转移这是一种有机物质的有机物质.球形形状的球形状

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