title: CD44 and CD24 coordinate the reprogramming of nasopharyngeal carcinoma cells towards a cancer stem cell phenotype through STAT3 activation.
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.
authors: Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan.
authors: Yao-An
authors: YA
authors: Shen
authors: Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan.
authors: Chia-Yu
authors: CY
authors: Wang
authors: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei 112, Taiwan.
authors: Hui-Yen
authors: HY
authors: Chuang
authors: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei 112, Taiwan.
authors: John Jeng-Jong
authors: JJ
authors: Hwang
authors: Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan.
authors: Wei-Hsin
authors: WH
authors: Chi
authors: Department of Otorhinolaryngology, Taipei Veterans General Hospital, Taipei 112, Taiwan.
authors: Chih-Hung
authors: CH
authors: Shu
authors: Department of Otorhinolaryngology, Taipei Veterans General Hospital, Taipei 112, Taiwan.
authors: Ching-Yin
authors: CY
authors: Ho
authors: Department of Pathology, Taipei Veterans General Hospital, Taipei 112, Taiwan.
authors: Wing-Yin
authors: WY
authors: Li
authors: Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan.|Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan.|Department of Pediatrics, Taipei City Hospital, Renai Branch, Taipei 106, Taiwan.
authors: Yann-Jang
authors: YJ
authors: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis; D051927:CD24 Antigen / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D065150:Cellular Reprogramming; D004307:Dose-Response Relationship, Radiation; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism*; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D010641:Phenotype; D050796:STAT3 Transcription Factor / Q000378:metabolism*
chemical_list: D051927:CD24 Antigen; C497889:CD24 protein, human; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human
keywords: CD24; CD44; STAT3; cancer stem cell; nasopharyngeal carcinoma