Doxycycline inducible Kruppel-like factor 4 lentiviral vector mediates mesenchymal to epithelial transition in ovarian cancer cells

Zixuan Chen, Yinan Wang, Wen Liu, Guannan Zhao, Sue Lee, Andrea Balogh, Yanan Zou, Yuqi Guo, Zhan Zhang, Weiwang Gu, Chengyao Li, Gabor Tigyi, Junming Yue

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Abstract

Ovarian cancer presents therapeutic challenges due to its typically late detection, aggressive metastasis, and therapeutic resistance. The transcription factor Krüppel-like factor 4 (KLF4) has been implicated in human cancers as a tumor suppressor or oncogene, although its role depends greatly on the cellular context. The role of KLF4 in ovarian cancer has not been elucidated in mechanistic detail. In this study, we investigated the role of KLF4 in ovarian cancer cells by transducing the ovarian cancer cell lines SKOV3 and OVCAR3 with a doxycycline-inducible KLF4 lentiviral vector. Overexpression of KLF4 reduced cell proliferation, migration, and invasion. The epithelial cell marker gene E-cadherin was significantly upregulated, whereas the mesenchymal cell marker genes vimentin, twist1and snail2 (slug) were downregulated in both KLF4-expressing SKOV3 and OVCAR3 cells. KLF4 inhibited the transforming growth factor β (TGFβ)-induced epithelial to mesenchymal transition (EMT) in ovarian cancer cells. Taken together, our data demonstrate that KLF4 functions as a tumor suppressor gene in ovarian cancer cells by inhibiting TGFβ-induced EMT.

Original languageEnglish (US)
Article numbere105331
JournalPLoS ONE
Volume9
Issue number8
DOIs
StatePublished - Aug 19 2014

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doxycycline
Epithelial-Mesenchymal Transition
ovarian neoplasms
Doxycycline
Ovarian Neoplasms
Cells
Genes
Transforming Growth Factors
Tumors
transforming growth factors
Cell proliferation
Vimentin
Cadherins
therapeutics
Gastropoda
neoplasms
genetic markers
tumor suppressor genes
Transcription Factors
cadherins

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Doxycycline inducible Kruppel-like factor 4 lentiviral vector mediates mesenchymal to epithelial transition in ovarian cancer cells. / Chen, Zixuan; Wang, Yinan; Liu, Wen; Zhao, Guannan; Lee, Sue; Balogh, Andrea; Zou, Yanan; Guo, Yuqi; Zhang, Zhan; Gu, Weiwang; Li, Chengyao; Tigyi, Gabor; Yue, Junming.

In: PLoS ONE, Vol. 9, No. 8, e105331, 19.08.2014.

Research output: Contribution to journalArticle

Chen, Zixuan ; Wang, Yinan ; Liu, Wen ; Zhao, Guannan ; Lee, Sue ; Balogh, Andrea ; Zou, Yanan ; Guo, Yuqi ; Zhang, Zhan ; Gu, Weiwang ; Li, Chengyao ; Tigyi, Gabor ; Yue, Junming. / Doxycycline inducible Kruppel-like factor 4 lentiviral vector mediates mesenchymal to epithelial transition in ovarian cancer cells. In: PLoS ONE. 2014 ; Vol. 9, No. 8.
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