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 language | English |
|---|---|
| Pages (from-to) | 58351-58366 |
| Number of pages | 16 |
| Journal | Oncotarget |
| Volume | 7 |
| Issue number | 36 |
| DOIs | |
| Publication status | Published - Sep 6 2016 |
| Externally published | Yes |
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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
Cite this
CD44 and CD24 coordinate the reprogramming of nasopharyngeal carcinoma cells towards a cancer stem cell phenotype through STAT3 activation. / Shen, Yao-An; Wang, Chia-Yu; Chuang, Hui-Yen; Hwang, John Jeng-Jong; Chi, Wei-Hsin; Shu, Chih-Hung; Ho, Ching-Yin; Li, Wing-Yin; Chen, Yann-Jang.
In: Oncotarget, Vol. 7, No. 36, 06.09.2016, p. 58351-58366.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - CD44 and CD24 coordinate the reprogramming of nasopharyngeal carcinoma cells towards a cancer stem cell phenotype through STAT3 activation
AU - Shen, Yao-An
AU - Wang, Chia-Yu
AU - Chuang, Hui-Yen
AU - Hwang, John Jeng-Jong
AU - Chi, Wei-Hsin
AU - Shu, Chih-Hung
AU - Ho, Ching-Yin
AU - Li, Wing-Yin
AU - Chen, Yann-Jang
PY - 2016/9/6
Y1 - 2016/9/6
N2 - 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.
AB - 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.
KW - Animals
KW - Apoptosis
KW - CD24 Antigen/metabolism
KW - Carcinoma/metabolism
KW - Cell Differentiation
KW - Cell Line, Tumor
KW - Cell Membrane/metabolism
KW - Cellular Reprogramming
KW - Dose-Response Relationship, Radiation
KW - Epithelial-Mesenchymal Transition
KW - Humans
KW - Hyaluronan Receptors/metabolism
KW - Mice
KW - Mice, Inbred NOD
KW - Mice, SCID
KW - Nasopharyngeal Carcinoma
KW - Nasopharyngeal Neoplasms/metabolism
KW - Neoplasm Transplantation
KW - Neoplastic Stem Cells/metabolism
KW - Phenotype
KW - STAT3 Transcription Factor/metabolism
U2 - 10.18632/oncotarget.11113
DO - 10.18632/oncotarget.11113
M3 - Article
C2 - 27521216
VL - 7
SP - 58351
EP - 58366
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 36
ER -