title: Doxycycline inducible Krüppel-like factor 4 lentiviral vector mediates mesenchymal to epithelial transition in ovarian cancer cells.
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.
authors.affiliation: 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.
authors.forename: Zixuan
authors.initials: Z
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Yinan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Wen
authors.initials: W
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Guannan
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
authors.forename: Suechin
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
authors.forename: Andrea
authors.initials: A
authors.lastname: Balogh
authors.affiliation: The Second Affiliated Hospital of Harbin Medical University, Harbin, P. R. China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Zou
authors.affiliation: The Third Affiliated Hospital, Zhengzhou University, Zhengzhou, P. R. China.
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Guo
authors.affiliation: The Third Affiliated Hospital, Zhengzhou University, Zhengzhou, P. R. China.
authors.forename: Zhan
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
authors.forename: Weiwang
authors.initials: W
authors.lastname: Gu
authors.affiliation: Southern Medical University, Guangzhou, P. R. China.
authors.forename: Chengyao
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
authors.forename: Gabor
authors.initials: G
authors.lastname: Tigyi
authors.affiliation: 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.
authors.forename: Junming
authors.initials: J
authors.lastname: Yue
mesh_terms: D002465:Cell Movement; D049109:Cell Proliferation; D004318:Doxycycline / Q000494:pharmacology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics* / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics; D061986:MCF-7 Cells; D010051:Ovarian Neoplasms; D015533:Transcriptional Activation; D016212:Transforming Growth Factor beta / Q000502:physiology
chemical_list: C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D016212:Transforming Growth Factor beta; D004318:Doxycycline