[RETRACTED] ERK1/2-Nanog signaling pathway enhances CD44(+) cancer stem-like cell phenotypes and epithelial-to-mesenchymal transition in head and neck squamous cell carcinomas Journal Article

   

Authors:	Huang, C.; Yoon, C.; Zhou, X. H.; Zhou, Y. C.; Zhou, W. W.; Liu, H.; Yang, X.; Lu, J.; Lee, S. Y.; Huang, K.
Article Title:	[RETRACTED] ERK1/2-Nanog signaling pathway enhances CD44(+) cancer stem-like cell phenotypes and epithelial-to-mesenchymal transition in head and neck squamous cell carcinomas
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. © 2020, The Author(s).
Journal Title:	Cell Death & Disease
Volume:	11
ISSN:	2041-4889
Publisher:	Nature Publishing Group
Date Published:	2020-04-23
Start Page:	266
Language:	English
DOI:	10.1038/s41419-020-2448-6
PUBMED:	32327629
PROVIDER:	scopus
PMCID:	PMC7181750
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85083831724&doi=10.1038%2fs41419-020-2448-6&partnerID=40&md5=b548848b588a97e72642c987d142a3a4
Notes:	Article -- Retraction issued, see DOI: 10.1038/s41419-024-06608-7 -- Source: Scopus

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