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

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Title: Knockout of MTF1 Inhibits the Epithelial to Mesenchymal Transition in Ovarian Cancer Cells
Authors: Ji, Liang Browse this author
Zhao, Guannan Browse this author
Zhang, Peng Browse this author
Huo, Wenying Browse this author
Dong, Peixin Browse this author →KAKEN DB
Watari, Hidemichi Browse this author →KAKEN DB
Jia, Limin Browse this author
Pfeffer, Lawrence M Browse this author
Yue, Junming Browse this author
Zheng, Jinhua Browse this author
Keywords: MTF1
CRISPR/Cas9 nickase
lentiviral vector
ovarian cancer
epithelial to mesenchymal transition
Issue Date: 2018
Publisher: Ivyspring International Publisher
Journal Title: Journal of Cancer
Volume: 9
Issue: 24
Start Page: 4578
End Page: 4585
Publisher DOI: 10.7150/jca.28040
Abstract: 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.
Type: article
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 董 培新

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