EIF5A2 controls ovarian tumor growth and metastasis by promoting epithelial to mesenchymal transition via the TGFβ pathway

Zhao, Guannan; Zhang, Wenjing; Dong, Peixin; Watari, Hidemichi; Guo, Yuqi; Pfeffer, Lawrence M; Tigyi, Gabor; Yue, Junming

EIF5A2 controls ovarian tumor growth and metastasis by promoting epithelial to mesenchymal transition via the TGFβ pathway

Zhao, Guannan; Zhang, Wenjing; Dong, Peixin et al.

Cell & Bioscience, 2021, 11, 70

Permalink : https://hdl.handle.net/2115/80967

このアイテムのアクセス数:558件（2026-08-27 06:18 集計）

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アクセス権	open access
URI	https://hdl.handle.net/2115/80967
タイトル	EIF5A2 controls ovarian tumor growth and metastasis by promoting epithelial to mesenchymal transition via the TGFβ pathway
著者	Zhao, Guannan ; Zhang, Wenjing ; Dong, Peixin ; Watari, Hidemichi ; Guo, Yuqi ; Pfeffer, Lawrence M ; Tigyi, Gabor ; Yue, Junming
著者名 Zhao, Guannan
著者名 Zhang, Wenjing
e-Rad_Researcher 50602504 著者名 Dong, Peixin
e-Rad_Researcher 10344508 著者名 Watari, Hidemichi
著者名 Guo, Yuqi
著者名 Pfeffer, Lawrence M
著者名 Tigyi, Gabor
著者名 Yue, Junming
言語	英語
キーワード	EIF5A2
	CRISPR
	Cas9 nickase
	Lentiviral vector
	Ovarian cancer
	Epithelial to mesenchymal transition
	Orthotopic ovarian cancer mouse model
発行日	2021-04-07
出版者	BioMed Central
収録物名	Cell & Bioscience
巻(号)	11
ページ	70
抄録	Background: Epithelial to mesenchymal transition (EMT) contributes to tumor metastasis and chemoresistance. Eukaryotic initiation factor 5A2 (EIF5A2) is highly expressed in a variety of human cancers but rarely expressed in normal tissues. While EIF5A2 has oncogenic activity in several cancers and contributes to tumor metastasis, its role in ovarian cancer is unknown. In this study, we investigate whether EIF5A2 contributes to ovarian tumor metastasis by promoting EMT. Methods: To investigate the role of EIF5A2, we knocked out (KO) EIF5A2 using lentiviral CRISPR/Cas9 nickase in high invasive SKOV3 and OVCAR8 cells and overexpressed EIF5A2 in low invasive OVCAR3 cells using lentiviral vector. Cell proliferation, migration and invasion was examined in vitro ovarian cancer cells and tumor metastasis was evaluated in vivo using orthotopic ovarian cancer mouse models. Results: Here we report that EIF5A2 is highly expressed in ovarian cancers and associated with patient poor survival. Lentiviral CRISPR/Cas9 nickase vector mediated knockout (KO) of EIF5A2 inhibits epithelial to mesenchymal transition (EMT) in SKOV3 and OVCAR8 ovarian cancer cells that express high levels of EIF5A2. In contrast, overexpression of EIF5A2 promotes EMT in OVCAR3 epithelial adenocarcinoma cells that express relatively low EIF5A2 levels. KO of EIF5A2 in SKOV3 and OVCAR8 cells inhibits ovarian cancer cell migration and invasion, while its overexpression promotes cell migration and invasion in OVCAR3 adenocarcinoma cells. We further demonstrate that EIF5A2 promotes EMT by activating the TGFβ pathway and KO of EIF5A2 inhibits ovarian tumor growth and metastasis in orthotopic ovarian cancer mouse models. Conclusion: Our results indicate that EIF5A2 is an important controller of ovarian tumor growth and metastasis by promoting EMT and activating the TGFβ pathway.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
権利情報	Creative Commons Attribution 4.0 International
PISSN	2045-3701
関連情報	PMID 33827661
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.1186/s13578-021-00578-5