Doxycycline inducible Krüppel-like factor 4 lentiviral vector mediates mesenchymal to epithelial transition in ovarian cancer cells
Authors: Suechin Lee
Andrea Balogh
Yuqi Guo
Weiwang Gu
Wen Liu
Guannan Zhao
Chengyao Li
Yanan Zou
Gabor Tigyi
Zhan Zhang
Zixuan Chen
Yinan Wang
Junming Yue
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: Ovarian cancer; KLF4; tumor suppressor; oncogene; cell proliferation
Affiliations: Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America; Center for Cancer Research, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America; Southern Medical University, Guangzhou, P. R. China., Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America; Center for Cancer Research, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America; Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America., Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America; Center for Cancer Research, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America; The Third Affiliated Hospital, Zhengzhou University, Zhengzhou, P. R. China., Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America., The Second Affiliated Hospital of Harbin Medical University, Harbin, P. R. China., The Third Affiliated Hospital, Zhengzhou University, Zhengzhou, P. R. China., Southern Medical University, Guangzhou, P. R. China., Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America; Center for Cancer Research, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.

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, twist1 and 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. 

Retracted: No

PubPeer comments:
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