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.
Highlights
Ovarian cancer has a high mortality rate, reportedly causes 15,000 deaths annually in the US [1]
We investigated the role of Kruppel-like factor 4 (KLF4) in ovarian cancer cells using a doxycycline (Dox)-dependent KLF4-inducible lentiviral vector (Tet-on) and found that inducible overexpression of KLF4 reduced cell proliferation, migration, and invasion through promoting mesenchymal to epithelial transition (MET) in ovarian cancer cells
To examine the induced expression of KLF4 and EGFP in the ovarian cancer cell lines SKOV3 and OVCAR3, Dox was added at a final concentration of 1 mg/ml, and the expression of KLF4 and EGFP at different time points was detected by Western blot
Summary
Ovarian cancer has a high mortality rate, reportedly causes 15,000 deaths annually in the US [1]. In colon and prostate cancer, KLF4 acts as an oncogene [5,6]. It plays a tumor suppressor role in neuroblastoma, lung cancer, gastric cancer, lymphoma, cervical cancer, pancreatic ductal cancer, and hepatocellular carcinoma [7,8,9,10,11,12,13]. KLF4 can function both as an oncogene [14,15] and a tumor suppressor [16,17,18]. The role of KLF4 in ovarian cancer has not been adequately and mechanistically addressed. A previous study indicates that the expression level of KLF4 was significantly reduced in ovarian cancer compared to normal ovarian epithelium, suggesting that KLF4 might potentially act as a tumor suppressor in ovarian cancer [19]
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