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Klf4 reduces stemness phenotype, triggers mesenchymal-epithelial transition (MET)-like molecular changes, and prevents tumor progression in nasopharygeal carcinoma

The reprogramming factor Krüppel-like factor 4 (Klf4), one of the Yamanaka's reprogramming factors, plays an essential role in reprogramming somatic cells into induced pluripotent stem cells (iPSCs). Klf4 is dysregulated and displays divergent functions in multiple malignancies, but the biologi...

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Autores principales: Li, Xiqing, Zhao, Zhunlan, Zhang, Xiaoling, Yang, Sheng, Lin, Xia, Yang, Xinglong, Lin, Xiaolin, Shi, Junwen, Wang, Shengchun, Zhao, Wentao, Li, Jing, Gao, Fei, Liu, Mingyue, Ma, Ning, Luo, Weiren, Yao, Kaitai, Sun, Yan, Xiao, Shengjun, Xiao, Dong, Jia, Junshuang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5706845/
https://www.ncbi.nlm.nih.gov/pubmed/29212199
http://dx.doi.org/10.18632/oncotarget.21370
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author Li, Xiqing
Zhao, Zhunlan
Zhang, Xiaoling
Yang, Sheng
Lin, Xia
Yang, Xinglong
Lin, Xiaolin
Shi, Junwen
Wang, Shengchun
Zhao, Wentao
Li, Jing
Gao, Fei
Liu, Mingyue
Ma, Ning
Luo, Weiren
Yao, Kaitai
Sun, Yan
Xiao, Shengjun
Xiao, Dong
Jia, Junshuang
author_facet Li, Xiqing
Zhao, Zhunlan
Zhang, Xiaoling
Yang, Sheng
Lin, Xia
Yang, Xinglong
Lin, Xiaolin
Shi, Junwen
Wang, Shengchun
Zhao, Wentao
Li, Jing
Gao, Fei
Liu, Mingyue
Ma, Ning
Luo, Weiren
Yao, Kaitai
Sun, Yan
Xiao, Shengjun
Xiao, Dong
Jia, Junshuang
author_sort Li, Xiqing
collection PubMed
description The reprogramming factor Krüppel-like factor 4 (Klf4), one of the Yamanaka's reprogramming factors, plays an essential role in reprogramming somatic cells into induced pluripotent stem cells (iPSCs). Klf4 is dysregulated and displays divergent functions in multiple malignancies, but the biological roles of Klf4 in nasopharyngeal carcinoma (NPC) remain unknown. The present study revealed that Klf4 downregulation in a cohort of human NPC biopsies is significantly associated with invasive and metastatic phenotypes of NPC. Our results showed exogenous expression of Klf4 significantly inhibited cell proliferation, decreased stemness, triggered mesenchymal-epithelial transition (MET)-like molecular changes, and suppressed migration and invasion of NPC cells, whereas depletion of endogeneous Klf4 by RNAi reversed the aforementioned biological behaviors and characheristics. Klf4 silencing significantly enhanced the metastatic ability of NPC cells in vivo. In addition, CHIP assay confirmed that E-cadherin is a transcriptional target of Klf4 in NPC cells. Additional studies demonstrated that Klf4-induced MET-like cellular marker alterations, and reduced motility and invasion of NPC cells were mediated by E-cadherin. This study revealed the clinical correlation between Klf4 expression and epithelial-mesenchymal transition (EMT) biomarkers (including its target gene E-cadherin) in a cohort of NPC biopsies. Taken together, our findings suggest, for what we believe is the first time, that Klf4 functions as a tumor suppressor in NPC to decrease stemness phenotype, inhibit EMT and prevent tumor progression, suggesting that restoring Klf4 function may provide therapeutic benefits in NPC.
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spelling pubmed-57068452017-12-05 Klf4 reduces stemness phenotype, triggers mesenchymal-epithelial transition (MET)-like molecular changes, and prevents tumor progression in nasopharygeal carcinoma Li, Xiqing Zhao, Zhunlan Zhang, Xiaoling Yang, Sheng Lin, Xia Yang, Xinglong Lin, Xiaolin Shi, Junwen Wang, Shengchun Zhao, Wentao Li, Jing Gao, Fei Liu, Mingyue Ma, Ning Luo, Weiren Yao, Kaitai Sun, Yan Xiao, Shengjun Xiao, Dong Jia, Junshuang Oncotarget Research Paper The reprogramming factor Krüppel-like factor 4 (Klf4), one of the Yamanaka's reprogramming factors, plays an essential role in reprogramming somatic cells into induced pluripotent stem cells (iPSCs). Klf4 is dysregulated and displays divergent functions in multiple malignancies, but the biological roles of Klf4 in nasopharyngeal carcinoma (NPC) remain unknown. The present study revealed that Klf4 downregulation in a cohort of human NPC biopsies is significantly associated with invasive and metastatic phenotypes of NPC. Our results showed exogenous expression of Klf4 significantly inhibited cell proliferation, decreased stemness, triggered mesenchymal-epithelial transition (MET)-like molecular changes, and suppressed migration and invasion of NPC cells, whereas depletion of endogeneous Klf4 by RNAi reversed the aforementioned biological behaviors and characheristics. Klf4 silencing significantly enhanced the metastatic ability of NPC cells in vivo. In addition, CHIP assay confirmed that E-cadherin is a transcriptional target of Klf4 in NPC cells. Additional studies demonstrated that Klf4-induced MET-like cellular marker alterations, and reduced motility and invasion of NPC cells were mediated by E-cadherin. This study revealed the clinical correlation between Klf4 expression and epithelial-mesenchymal transition (EMT) biomarkers (including its target gene E-cadherin) in a cohort of NPC biopsies. Taken together, our findings suggest, for what we believe is the first time, that Klf4 functions as a tumor suppressor in NPC to decrease stemness phenotype, inhibit EMT and prevent tumor progression, suggesting that restoring Klf4 function may provide therapeutic benefits in NPC. Impact Journals LLC 2017-09-27 /pmc/articles/PMC5706845/ /pubmed/29212199 http://dx.doi.org/10.18632/oncotarget.21370 Text en Copyright: © 2017 Li et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Li, Xiqing
Zhao, Zhunlan
Zhang, Xiaoling
Yang, Sheng
Lin, Xia
Yang, Xinglong
Lin, Xiaolin
Shi, Junwen
Wang, Shengchun
Zhao, Wentao
Li, Jing
Gao, Fei
Liu, Mingyue
Ma, Ning
Luo, Weiren
Yao, Kaitai
Sun, Yan
Xiao, Shengjun
Xiao, Dong
Jia, Junshuang
Klf4 reduces stemness phenotype, triggers mesenchymal-epithelial transition (MET)-like molecular changes, and prevents tumor progression in nasopharygeal carcinoma
title Klf4 reduces stemness phenotype, triggers mesenchymal-epithelial transition (MET)-like molecular changes, and prevents tumor progression in nasopharygeal carcinoma
title_full Klf4 reduces stemness phenotype, triggers mesenchymal-epithelial transition (MET)-like molecular changes, and prevents tumor progression in nasopharygeal carcinoma
title_fullStr Klf4 reduces stemness phenotype, triggers mesenchymal-epithelial transition (MET)-like molecular changes, and prevents tumor progression in nasopharygeal carcinoma
title_full_unstemmed Klf4 reduces stemness phenotype, triggers mesenchymal-epithelial transition (MET)-like molecular changes, and prevents tumor progression in nasopharygeal carcinoma
title_short Klf4 reduces stemness phenotype, triggers mesenchymal-epithelial transition (MET)-like molecular changes, and prevents tumor progression in nasopharygeal carcinoma
title_sort klf4 reduces stemness phenotype, triggers mesenchymal-epithelial transition (met)-like molecular changes, and prevents tumor progression in nasopharygeal carcinoma
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5706845/
https://www.ncbi.nlm.nih.gov/pubmed/29212199
http://dx.doi.org/10.18632/oncotarget.21370
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