Oncotarget

Research Papers:

CD44 and CD24 coordinate the reprogramming of nasopharyngeal carcinoma cells towards a cancer stem cell phenotype through STAT3 activation

Yao-An Shen, Chia-Yu Wang, Hui-Yen Chuang, John Jeng-Jong Hwang, Wei-Hsin Chi, Chih-Hung Shu, Ching-Yin Ho, Wing-Yin Li _ and Yann-Jang Chen

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Oncotarget. 2016; 7:58351-58366. https://doi.org/10.18632/oncotarget.11113

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Abstract

Yao-An Shen1, Chia-Yu Wang2, Hui-Yen Chuang3, John Jeng-Jong Hwang3, Wei-Hsin Chi2, Chih-Hung Shu5, Ching-Yin Ho5, Wing-Yin Li6, Yann-Jang Chen2,4,7

1Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan

2Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan

3Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei 112, Taiwan

4Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan

5Department of Otorhinolaryngology, Taipei Veterans General Hospital, Taipei 112, Taiwan

6Department of Pathology, Taipei Veterans General Hospital, Taipei 112, Taiwan

7Department of Pediatrics, Taipei City Hospital, Renai Branch, Taipei 106, Taiwan

Correspondence to:

Yann-Jang Chen, email: yjchen@ym.edu.tw

Keywords: nasopharyngeal carcinoma, cancer stem cell, CD44, CD24, STAT3

Received: December 08, 2015    Accepted: July 26, 2016    Published: August 8, 2016

ABSTRACT

Cell surface proteins such as CD44 and CD24 are used to distinguish cancer stem cells (CSCs) from the bulk-tumor population. However, the molecular functionalities of CD24 and CD44, and how these two molecules coordinate in CSCs remain poorly understood. We found that nasopharyngeal carcinoma (NPC) cells with high expression of CD44 and CD24 proteins presented with pronounced CSC properties. Accordingly, a subpopulation of NPC cells with co-expression of CD44 and CD24 were specially enriched in high-stage clinical samples. Furthermore, ectopically expressing the epithelial-mesenchymal transition (EMT) regulator Twist was able to upregulate the stemness factors, and vice versa. This indicates a reciprocal regulation of stemness and EMT. Intriguingly, we found that this reciprocal regulation was differentially orchestrated by CD44 and CD24, and only simultaneous silencing the expression of CD44 and CD24 led to a broad-spectrum suppression of CSC properties. Oppositely, overexpression of CD44 and CD24 induced the reprogramming of parental NPC cells into CSCs through STAT3 activation, which could be blunted by STAT3 inhibition, indicating that CD44 and CD24 collaboratively drive the reprogramming of NPC cells through STAT3-mediated stemness and EMT activation. Consequently, targeting of the CD44/CD24/STAT3 axis may provide a potential therapeutic paradigm for the treatment of NPC through repressing CSC activities.


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