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

研究成果: 雜誌貢獻文章

13 引文 (Scopus)

摘要

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.
原文英語
頁(從 - 到)58351-58366
頁數16
期刊Oncotarget
7
發行號36
DOIs
出版狀態已發佈 - 九月 6 2016
對外發佈Yes

指紋

Neoplastic Stem Cells
Phenotype
Epithelial-Mesenchymal Transition
Nasopharyngeal carcinoma
Membrane Proteins
Up-Regulation
Population
Neoplasms
Proteins

引用此文

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.

於: Oncotarget, 卷 7, 編號 36, 06.09.2016, p. 58351-58366.

研究成果: 雜誌貢獻文章

Shen, Y-A, Wang, C-Y, Chuang, H-Y, Hwang, JJ-J, Chi, W-H, Shu, C-H, Ho, C-Y, Li, W-Y & Chen, Y-J 2016, 'CD44 and CD24 coordinate the reprogramming of nasopharyngeal carcinoma cells towards a cancer stem cell phenotype through STAT3 activation', Oncotarget, 卷 7, 編號 36, 頁 58351-58366. https://doi.org/10.18632/oncotarget.11113
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. / CD44 and CD24 coordinate the reprogramming of nasopharyngeal carcinoma cells towards a cancer stem cell phenotype through STAT3 activation. 於: Oncotarget. 2016 ; 卷 7, 編號 36. 頁 58351-58366.
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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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author = "Yao-An Shen and Chia-Yu Wang and Hui-Yen Chuang and Hwang, {John Jeng-Jong} and Wei-Hsin Chi and Chih-Hung Shu and Ching-Yin Ho and Wing-Yin Li and Yann-Jang Chen",
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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 -