Department of Obstetrics and Gynecology, Nanhai Hospital Affiliated to Southern Medical University, Foshan 528200, Guangdong, China.
Department of Hematology, Shunde Hospital of Southem Medical University (The First People's Hospital of Shunde), Foshan 528308, Guangdong, China.
Biomed Environ Sci. 2021 Feb 20;34(2):139-151. doi: 10.3967/bes2021.020.
The underlying mechanism of Ezrin in ovarian cancer (OVCA) is far from being understood. Therefore, this study aimed to assess the role of Ezrin in OVCA cells (SKOV3 and CaOV3) and investigate the associated molecular mechanisms.
We performed Western blotting, reverse transcription-quantitative polymerase chain reaction, MTT, cell colony, cell wound healing, transwell migration and invasion, RhoA and Rac active pull down assays, and confocal immunofluorescence experiments to evaluate the functions and molecular mechanisms of Ezrin overexpression or knockdown in the proliferation and metastasis of OVCA cells.
The ectopic expression of Ezrin significantly increased cell proliferation, invasiveness, and epithelial-mesenchymal transition (EMT) in OVCA cells. By contrast, the knockdown of endogenous Ezrin prevented OVCA cell proliferation, invasiveness, and EMT. Lastly, we observed that Ezrin can positively regulate the active forms of RhoA rather than Rac-1 in OVCA cells, thereby promoting robust stress fiber formation.
Our results indicated that Ezrin regulates OVCA cell proliferation and invasiveness by modulating EMT and induces actin stress fiber formation by regulating Rho-GTPase activity, which provides novel insights into the treatment of the OVCA.
Ezrin 在卵巢癌(OVCA)中的作用机制尚不清楚。因此,本研究旨在评估 Ezrin 在 OVCA 细胞(SKOV3 和 CaOV3)中的作用,并探讨相关的分子机制。
我们通过 Western blot、逆转录定量聚合酶链反应(RT-qPCR)、MTT 法、细胞集落形成、细胞划痕愈合、Transwell 迁移和侵袭实验、RhoA 和 Rac 活性下拉实验以及共聚焦免疫荧光实验,评估 Ezrin 过表达或敲低对 OVCA 细胞增殖和转移的功能和分子机制。
Ezrin 的异位表达显著增加了 OVCA 细胞的增殖、侵袭和上皮间质转化(EMT)。相比之下,内源性 Ezrin 的敲低可阻止 OVCA 细胞的增殖、侵袭和 EMT。最后,我们观察到 Ezrin 可以在 OVCA 细胞中正向调节 RhoA 的活性形式,而不是 Rac-1,从而促进肌动蛋白应力纤维的形成。
我们的研究结果表明,Ezrin 通过调节 EMT 调节 OVCA 细胞的增殖和侵袭,并通过调节 Rho-GTPase 活性诱导肌动蛋白应力纤维形成,这为 OVCA 的治疗提供了新的见解。