Research Papers:

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

Xiqing Li, Zhunlan Zhao, Xiaoling Zhang, Sheng Yang, Xia Lin, Xinglong Yang, Xiaolin Lin, Junwen Shi, Shengchun Wang, Wentao Zhao, Jing Li, Fei Gao, Mingyue Liu, Ning Ma, Weiren Luo, Kaitai Yao, Yan Sun, Shengjun Xiao, Dong Xiao _ and Junshuang Jia

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Oncotarget. 2017; 8:93924-93941. https://doi.org/10.18632/oncotarget.21370

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Xiqing Li1,2,3,*, Zhunlan Zhao1,3,*, Xiaoling Zhang4,*, Sheng Yang1,*, Xia Lin1, Xinglong Yang1, Xiaolin Lin1, Junwen Shi1, Shengchun Wang1, Wentao Zhao1, Jing Li1, Fei Gao1,7, Mingyue Liu3, Ning Ma3, Weiren Luo8, Kaitai Yao1, Yan Sun6, Shengjun Xiao5, Dong Xiao1,2 and Junshuang Jia1

1Guangdong Provincial Key Laboratory of Cancer Immunotherapy Research and Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, Southern Medical University, Guangzhou 510515, China

2Institute of Comparative Medicine & Laboratory Animal Center, Southern Medical University, Guangzhou 510515, China

3Department of Oncology, The People’s Hosptial of Zhengzhou University, Zhengzhou 450003, China

4Department of Physiology, Faculty of Basic Medical Sciences, Guilin Medical University, Guilin 541004, China

5Department of Pathology, The Second Affiliated Hospital, Guilin Medical University, Guilin 541199, China

6Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China

7Department of Gastroenterology, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China

8The Third People's Hospital of Shenzhen, Guangdong Medical University, Shenzhen 518112, China

*These authors have contributed equally to this work

Correspondence to:

Dong Xiao, email: [email protected]

Shengjun Xiao, email: [email protected]

Junshuang Jia, email: [email protected]

Keywords: Klf4, nasopharyngeal carcinoma (NPC), stemness, epithelial-mesenchymal transition (EMT), cancer invasion and metastasis

Received: March 31, 2017     Accepted: June 29, 2017     Published: September 27, 2017


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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PII: 21370