Knockout of MTF1 inhibits the epithelial to mesenchymal transition in ovarian cancer cells

Liang Ji, Guannan Zhao, Peng Zhang, Wenying Huo, Peixin Dong, Hidemichi Watari, Limin Jia, Lawrence Pfeffer, Junming Yue, Jinhua Zheng

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)4578-4585
Number of pages8
JournalJournal of Cancer
Volume9
Issue number24
DOIs
StatePublished - Jan 1 2018

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Epithelial-Mesenchymal Transition
Ovarian Neoplasms
Transcription Factors
Metals
Neoplasm Metastasis
Clustered Regularly Interspaced Short Palindromic Repeats
Keratin-7
Recurrence
Catenins
Neoplasms
Survival
MAP Kinase Signaling System
Deoxyribonuclease I
Cadherins
Cell Movement
Early Diagnosis
Down-Regulation
Biomarkers
Epithelial Cells
Cell Proliferation

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Ji, L., Zhao, G., Zhang, P., Huo, W., Dong, P., Watari, H., ... Zheng, J. (2018). Knockout of MTF1 inhibits the epithelial to mesenchymal transition in ovarian cancer cells. Journal of Cancer, 9(24), 4578-4585. https://doi.org/10.7150/jca.28040

Knockout of MTF1 inhibits the epithelial to mesenchymal transition in ovarian cancer cells. / Ji, Liang; Zhao, Guannan; Zhang, Peng; Huo, Wenying; Dong, Peixin; Watari, Hidemichi; Jia, Limin; Pfeffer, Lawrence; Yue, Junming; Zheng, Jinhua.

In: Journal of Cancer, Vol. 9, No. 24, 01.01.2018, p. 4578-4585.

Research output: Contribution to journalArticle

Ji, L, Zhao, G, Zhang, P, Huo, W, Dong, P, Watari, H, Jia, L, Pfeffer, L, Yue, J & Zheng, J 2018, 'Knockout of MTF1 inhibits the epithelial to mesenchymal transition in ovarian cancer cells', Journal of Cancer, vol. 9, no. 24, pp. 4578-4585. https://doi.org/10.7150/jca.28040
Ji, Liang ; Zhao, Guannan ; Zhang, Peng ; Huo, Wenying ; Dong, Peixin ; Watari, Hidemichi ; Jia, Limin ; Pfeffer, Lawrence ; Yue, Junming ; Zheng, Jinhua. / Knockout of MTF1 inhibits the epithelial to mesenchymal transition in ovarian cancer cells. In: Journal of Cancer. 2018 ; Vol. 9, No. 24. pp. 4578-4585.
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