Piezo1通过驱动肌动蛋白细胞骨架重塑促进宫颈癌侵袭迁移的机制研究  

Mechanism of Piezo1-induced Actin Cytoskeleton Remodeling in Promoting the Metastasis of Cervical Cancer

作　　者：邓觉晓 李洋[1] 龚梦[1] 刘婷婷[1] 廖文欣 张蓝月 申复进[1] DENG Juexiao;LI Yang;GONG Meng(Renmin Hospital of Wuhan University,Hubei 430060,China)

机构地区：[1]武汉大学人民医院妇产科,430060

出　　处：《医学研究杂志》2024年第10期74-80,共7页Journal of Medical Research

基　　金：湖北省自然科学基金资助项目(2021CFB430)。

摘　　要：目的 探讨Piezo1通过驱动肌动蛋白细胞骨架重塑在宫颈癌侵袭迁移中的作用及机制。方法 采用免疫组化和Western blot法检测宫颈癌组织和细胞系中Piezo1和F-actin的表达;慢病毒转染沉默宫颈癌细胞系Siha及Hela中Piezo1基因,利用Transwell实验研究Piezo1对宫颈癌侵袭和迁移的影响,鬼笔环肽染色观察Piezo1对肌动蛋白细胞骨架的重塑作用,并进一步通过干预细胞骨架聚合状态以证实Piezo1影响宫颈癌侵袭迁移的机制。结果 宫颈癌组中Piezo1和F-actin表达量显著高于对照组,且有转移的宫颈癌组比无转移的宫颈癌组表达更高;沉默Piezo1下调了SiHa及HeLa细胞系中F-actin的表达,并抑制宫颈癌侵袭和迁移,这种抑制作用可被肌动蛋白聚合诱导剂Jasplakinolide部分解除,而激动Piezo1则上调F-actin表达,且促进宫颈癌侵袭和迁移,这种促进作用可被肌动蛋白解聚剂Latrunculin A所抑制。结论 Piezo1在宫颈癌中高表达,并驱动肌动蛋白细胞骨架重塑以促进宫颈癌侵袭和迁移。Objective To investigate the role and mechanism of Piezo1 in the invasion and migration of cervical cancer by driving actin cytoskeletal remodeling.Methods Immunohistochemistry and Western blot were used to detect the expression of Piezo1 and F-actin in cervical cancer tissues and cell lines;lentiviral transfection resulted in silencing of the Piezo1 gene in cervical cancer cell lines Siha and Hela,and the transwell assay was used to detect the effect of Piezo1 on the invasion and migration of cervical cancer.Phalloidin staining was used to observe the remodeling effect of Piezo1 on the actin cytoskeleton,and the mechanism of Piezo1 affecting the invasion and migration of cervical cancer was further confirmed by intervening in the cytoskeletal polymerization state.Results The expression levels of Piezo1 and F-actin in the cervical cancer group were significantly higher than those in the control group,and the expressions of Piezo1 and F-actin in the cervical cancer group were higher than that in the cervical cancer group without metastasis.Silencing Piezo1 downregulated the expressions of F-actin in SiHa and HeLa cell lines and inhibited cervical cancer invasion and migration,which was partially alleviated by the actin polymerization inducer Jasplakinolide,while the activation of Piezo1 upregulated F-actin expression and promoted the invasion and migration of cervical cancer,which could be inhibited by actin depolymerizer Latrunculin A.Conclusion Piezo1 is highly expressed in cervical cancer and drives actin cytoskeletal remodeling to promote the invasion and migration of cervical cancer.

关 键 词：宫颈癌 Piezo1 肌动蛋白细胞骨架 侵袭 迁移 

分 类 号：R711.74[医药卫生—妇产科学]