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, Yann-Jang Chen

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)58351-58366
Number of pages16
JournalOncotarget
Volume7
Issue number36
DOIs
Publication statusPublished - Sep 6 2016
Externally publishedYes

Keywords

  • Animals
  • Apoptosis
  • CD24 Antigen/metabolism
  • Carcinoma/metabolism
  • Cell Differentiation
  • Cell Line, Tumor
  • Cell Membrane/metabolism
  • Cellular Reprogramming
  • Dose-Response Relationship, Radiation
  • Epithelial-Mesenchymal Transition
  • Humans
  • Hyaluronan Receptors/metabolism
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms/metabolism
  • Neoplasm Transplantation
  • Neoplastic Stem Cells/metabolism
  • Phenotype
  • STAT3 Transcription Factor/metabolism

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