J Cancer 2018; 9(24):4578-4585. doi:10.7150/jca.28040

Research Paper

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

Liang Ji1, Guannan Zhao2,3, Peng Zhang2,3, Wenying Huo2,3, Peixin Dong4, Hidemichi Watari4, Limin Jia1, Lawrence M Pfeffer2,3, Junming Yue2,3✉, Jinhua Zheng1✉

1. Department of Anatomy, College of Basic Medical Science, Harbin Medical University, Harbin, China.
2. Department of Pathology and Laboratory Medicine, the University of Tennessee Health Science Center, Memphis, TN, 38163, USA.
3. Center for Cancer Research, University of Tennessee Health Science Center, Memphis, TN, 38163, USA.
4. Department of Obstetrics and Gynecology, Hokkaido University School of Medicine, Hokkaido University, Sapporo, Japan.

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Citation:
Ji L, Zhao G, Zhang P, Huo W, Dong P, Watari H, Jia L, Pfeffer LM, Yue J, Zheng J. Knockout of MTF1 Inhibits the Epithelial to Mesenchymal Transition in Ovarian Cancer Cells. J Cancer 2018; 9(24):4578-4585. doi:10.7150/jca.28040. Available from http://www.jcancer.org/v09p4578.htm

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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.

Keywords: MTF1, CRISPR/Cas9 nickase, lentiviral vector, ovarian cancer, epithelial to mesenchymal transition