Doxycycline Inducible Kruppel-Like Factor 4 Lentiviral Vector Mediates Mesenchymal to Epithelial Transition in Ovarian Cancer Cells

Krüppel-like factor 4 (KLF4) is an evolutionarily conserved zinc finger-containing transcription factor that regulates diverse cellular processes such as cell growth, proliferation, and differentiation. Since its discovery in 1996, KLF4 has been gaining a lot of attention, after it was shown in 2006 as one of four factors required for the induction of pluripotent stem cells (iPSCs). Here we review the current knowledge on the different functions and roles of KLF4 in various tissue and organ systems.

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“…The anti-EMT role of KLF4 was shown in other systems (147). In prostate cancer, three reports showed an opposite role for KLF4 in EMT.…”

Section: Roles In Diseasesmentioning

confidence: 76%

Krüppel-like factor 4 (KLF4): What we currently know

Ghaleb

Yang

2017

Gene

416

349

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“…TGFβ has been shown to induce EMT in ovarian cancer cells [46]. However, it is not clear how miR-203 regulates the TGFβ signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

miR-203 Functions as a Tumor Suppressor by Inhibiting Epithelial to Mesenchymal Transition in Ovarian Cancer

Zhao¹,

Guo

Chen

et al. 2015

J Cancer Sci Ther

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Objective Ovarian cancer is a gynecological malignancy that has a high mortality rate in women due to metastatic progression and recurrence. miRNAs are small, endogenous, noncoding RNAs that function as tumor suppressors or oncogenes in various human cancers by selectively suppressing the expression of target genes. The objective of this study is to investigate the role of miR-203 in ovarian cancer. Methods miR-203 was expressed in ovarian cancer SKOV3 and OVCAR3 cells using lentiviral vector and cell proliferation, migration, invasion were examined using MTT, transwell and Matrigel assays, respectively. Tumor growth was examined using Xenograft mouse model. Results miR-203 expression was downregulated, whereas expression of its target gene Snai2 was upregulated in human ovarian serous carcinoma tissue as compared to normal ovaries. In addition, high miR-203 expression was associated with long-term survival rate of ovarian cancer patients. miR-203 overexpression inhibited cell proliferation, migration, and invasion of SKOV3 and OVCAR3 ovarian cancer cells. Furthermore, miR-203 overexpression inhibited the epithelial to mesenchymal transition (EMT) in ovarian cancer cells. Silencing Snai2 with lentiviral short hairpin (sh) RNA mimics miR-203-mediated inhibition of EMT and tumor cell invasion. Xenografts of miR-203-overexpressing ovarian cancer cells in immunodeficient mice exhibited a significantly reduced tumor growth. Conclusion miR-203 functions as a tumor suppressor by down regulating Snai2 in ovarian cancer.

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“…The results from studies of epidermal cancer, hepatocellular carcinoma, breast cancer, pancreatic cancer, and prostate cancer with data predominantly originating from in vitro experiments show that KLF4 negatively regulates EMT (28)(29)(30)(31)(32)(33). On the other hand, KLF4's ability to regulate the stemness of cancer cells has been shown as an important factor in stimulating EMT in pancreatic, ovarian, endometrial, nasopharyngeal, prostate, and non-small lung cancers (34)(35)(36)(37)(38)(39)(40). Here, we demonstrate that KLF4 expression is positively correlated with epithelial markers of EMT in normal mucosa and negatively with mesenchymal markers in CRC.…”

Section: Discussionmentioning

confidence: 99%

Loss of the Krüppel-like factor 4 tumor suppressor is associated with epithelial-mesenchymal transition in colorectal cancer

Agbo

Huang

Ghaleb

et al. 2019

Preprint

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Colorectal cancer (CRC) is the third leading cancer-related cause of death due to its propensity to metastasize. Epithelial-mesenchymal transition (EMT) is a multistep process important for invasion and metastasis of CRC. Krüppel-like factor 4 (KLF4) is a zinc finger transcription factor highly expressed in differentiated cells of the intestinal epithelium. KLF4 has been shown to play a tumor suppressor role during CRC tumorigenesis -its loss accelerates development and progression of cancer. The present study examines the relationship between KLF4 and markers of EMT in CRC. Methods: Immunofluorescence staining for KLF4 and EMT markers was performed on archived patient samples after colorectal cancer resection and on colonic tissues of mice with colitis-associated cancer. Results: We found that KLF4 expression is lost in tumor sections obtained from CRC patients and in those of mouse colon following azoxymethane and dextran sodium sulfate (AOM/DSS) treatment when compared to their respective normal appearing mucosa. Importantly, in CRC patient tumor sections we observed a negative correlation between KLF4 levels and mesenchymal markers including TWIST, -catenin, claudin-1, Ncadherin, and vimentin. Similarly, in tumor tissues from AOM/DSS-treated mice KLF4 levels were negatively correlated with mesenchymal markers including SNAI2, -catenin, and vimentin and positively correlated with the epithelial marker E-cadherin. Conclusion: These findings suggest that the loss of KLF4 expression is a potentially significant indicator of EMT in CRC.

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Doxycycline Inducible Kruppel-Like Factor 4 Lentiviral Vector Mediates Mesenchymal to Epithelial Transition in Ovarian Cancer Cells

Cited by 47 publications

References 37 publications

Krüppel-like factor 4 (KLF4): What we currently know

Krüppel-like factor 4 (KLF4): What we currently know

miR-203 Functions as a Tumor Suppressor by Inhibiting Epithelial to Mesenchymal Transition in Ovarian Cancer

Loss of the Krüppel-like factor 4 tumor suppressor is associated with epithelial-mesenchymal transition in colorectal cancer

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