Knockout of MTF1 Inhibits the Epithelial to Mesenchymal Transition in Ovarian Cancer Cells

Ji, Liang; Zhao, Guannan; Zhang, Peng et al.

Journal of Cancer, 2018, 9(24), 4578-4585

Permalink : https://hdl.handle.net/2115/72342

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アクセス権
open access
URI
https://hdl.handle.net/2115/72342
タイトル
Knockout of MTF1 Inhibits the Epithelial to Mesenchymal Transition in Ovarian Cancer Cells
著者
Ji, Liang ; Zhao, Guannan ; Zhang, Peng ; Huo, Wenying ; Dong, Peixin ; Watari, Hidemichi ; Jia, Limin ; Pfeffer, Lawrence M ; Yue, Junming ; Zheng, Jinhua
著者名
Ji, Liang
著者名
Zhao, Guannan
著者名
Zhang, Peng
著者名
Huo, Wenying
e-Rad_Researcher
50602504
著者名
Dong, Peixin
e-Rad_Researcher
10344508
著者名
Watari, Hidemichi
著者名
Jia, Limin
著者名
Pfeffer, Lawrence M
著者名
Yue, Junming
著者名
Zheng, Jinhua
言語
英語
キーワード
MTF1
CRISPR/Cas9 nickase
lentiviral vector
ovarian cancer
epithelial to mesenchymal transition
発行日
2018
出版者
Ivyspring International Publisher
収録物名
Journal of Cancer
巻(号)
9(24)
ページ
4578-4585
抄録
Due to peritoneal metastasis and frequent recurrence, ovarian cancer has the highest mortality among gynecological cancers. Epithelial to mesenchymal transition (EMT) contributes to ovarian tumor metastasis. In this study, we report for the first time that metal regulatory transcription factor 1 (MTF1) was upregulated in ovarian cancer, and its high expression was associated with poor patient survival and disease relapse. Knockout of MTF1 using lentiviral CRISPR/Cas9 nickase vector-mediated gene editing inhibited EMT by upregulating epithelial cell markers E-cadherin and cytokeratin 7, and downregulating mesenchymal markers Snai2 and β-catenin in ovarian cancer SKOV3 and OVCAR3 cells. Loss of MTF1 reduced cell proliferation, migration, and invasion in both SKOV3 and OVCAR3 cells. Knockout of MTF1 upregulated the expression of the KLF4 transcription factor, and attenuated two cellular survival pathways, ERK1/2 and AKT. Our studies demonstrated that MTF1 plays an oncogenic role and contributes to ovarian tumor metastasis by promoting EMT. MTF1 may be a novel biomarker for early diagnosis as well as a drug target for clinical therapy.
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-NonCommercial 4.0 International
PISSN
1837-9664
関連情報 (isIdenticalTo)
出版社版DOI
https://doi.org/10.7150/jca.28040