ERK1/2-Nanog signaling pathway enhances CD44(+) cancer stem-like cell phenotypes and epithelial-to-mesenchymal transition in head and neck squamous cell carcinomas
DC Field | Value | Language |
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dc.contributor.author | Huang, Chuang | - |
dc.contributor.author | Yoon, Changhwan | - |
dc.contributor.author | Zhou, Xiao-Hong | - |
dc.contributor.author | Zhou, Ying-Chun | - |
dc.contributor.author | Zhou, Wen-Wen | - |
dc.contributor.author | Liu, Hong | - |
dc.contributor.author | Yang, Xin | - |
dc.contributor.author | Lu, Jun | - |
dc.contributor.author | Lee, Sei Young | - |
dc.contributor.author | Huang, Kun | - |
dc.date.available | 2020-08-04T03:21:03Z | - |
dc.date.issued | 2020-04 | - |
dc.identifier.issn | 2041-4889 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/42849 | - |
dc.description.abstract | Head and neck squamous cell carcinomas (HNSCCs) harbor a subset of cells that are CD44(+) and present with malignancy and radiotherapy resistance. As a key regulator of self-renewal, Nanog expression not only determines cell fate in pluripotent cells but also mediates tumorigenesis in cancer cells; thus, we examined the role of Nanog in CD44(+) HNSCC. Three HNSCC cell lines, tumor xenografts, and patient tumors were examined. Nanog levels were significantly higher in CD44(+) HNSCC spheroids than in CD44(-) spheroids, and further increased when grown as spheroids to enrich for CSCs. CD44(+) spheroids showed a 3.4-7.5-fold increase in migration and invasion compared with CD44(-) spheroids and were resistant to radiation therapy, which was reversed by inhibiting Nanog. Nanog knockdown also decreased spheroid formation by 66.5-68.8%. Moreover, a phosphokinase array identified upregulated ERK1/2 signaling in CD44(+) HNSCC cells compared with that in CD44(-) cells. ERK1/2 signaling was found to regulate Nanog expression, aiding tumor progression, metastasis, and radiotherapy resistance. In xenograft models, the combination of radiation and Nanog or ERK1/2 inhibition inhibited tumor growth by 75.6% and 79.1%, respectively. In lung metastasis models, CD44(+) cells injected into the tail vein of mice led to significantly more lung metastases and higher Nanog expression level compared with that by ERK1/2-knockdown CD44(+) cells. Finally, in tumor tissues, CD44 and Nanog expression levels were correlated with tumorigenesis in HNSCC patients. Thus, targeting Nanog and the ERK1/2 signaling pathway may prevent or reverse CSC phenotypes and epithelial-mesenchymal transition that drive tumor progression, metastasis, and radiotherapy resistance in HNSCC. | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | NATURE PUBLISHING GROUP | - |
dc.title | ERK1/2-Nanog signaling pathway enhances CD44(+) cancer stem-like cell phenotypes and epithelial-to-mesenchymal transition in head and neck squamous cell carcinomas | - |
dc.type | Article | - |
dc.identifier.doi | 10.1038/s41419-020-2448-6 | - |
dc.identifier.bibliographicCitation | CELL DEATH & DISEASE, v.11, no.4 | - |
dc.description.isOpenAccess | Y | - |
dc.identifier.wosid | 000530273000004 | - |
dc.identifier.scopusid | 2-s2.0-85083831724 | - |
dc.citation.number | 4 | - |
dc.citation.title | CELL DEATH & DISEASE | - |
dc.citation.volume | 11 | - |
dc.type.docType | Article | - |
dc.publisher.location | 영국 | - |
dc.subject.keywordPlus | RADIORESISTANCE | - |
dc.subject.keywordPlus | SUBPOPULATION | - |
dc.subject.keywordPlus | PROGRESSION | - |
dc.subject.keywordPlus | BIOLOGY | - |
dc.subject.keywordPlus | MARKER | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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