Ephrin A4-ephrin receptor A10 signaling promotes cell migration and spheroid formation by upregulating NANOG expression in oral squamous cell carcinoma cells

Abstract Ephrin type-A receptor 10 (EPHA10) has been implicated as a potential target for breast and prostate cancer therapy. However, its involvement in oral squamous cell carcinoma (OSCC) remains unclear. We demonstrated that EPHA10 supports in vivo tumor growth and lymphatic metastasis of OSCC ce...

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Autores principales:	Yu-Lin Chen, Yi-Chen Yen, Chuan-Wei Jang, Ssu-Han Wang, Hsin-Ting Huang, Chung-Hsing Chen, Jenn-Ren Hsiao, Jang-Yang Chang, Ya-Wen Chen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/21cf012a84ff48269dd235e08c02781b
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spelling	oai:doaj.org-article:21cf012a84ff48269dd235e08c02781b2021-12-02T15:23:06ZEphrin A4-ephrin receptor A10 signaling promotes cell migration and spheroid formation by upregulating NANOG expression in oral squamous cell carcinoma cells10.1038/s41598-020-80060-32045-2322https://doaj.org/article/21cf012a84ff48269dd235e08c02781b2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80060-3https://doaj.org/toc/2045-2322Abstract Ephrin type-A receptor 10 (EPHA10) has been implicated as a potential target for breast and prostate cancer therapy. However, its involvement in oral squamous cell carcinoma (OSCC) remains unclear. We demonstrated that EPHA10 supports in vivo tumor growth and lymphatic metastasis of OSCC cells. OSCC cell migration, epithelial mesenchymal transition (EMT), and sphere formation were found to be regulated by EPHA10, and EPHA10 was found to drive expression of some EMT- and stemness-associated transcription factors. Among EPHA10 ligands, exogenous ephrin A4 (EFNA4) induced the most OSCC cell migration and sphere formation, as well as up-regulation of SNAIL, NANOG, and OCT4. These effects were abolished by extracellular signal-regulated kinase (ERK) inhibition and NANOG knockdown. Also, EPHA10 was required for EFNA4-induced cell migration, sphere formation, and expression of NANOG and OCT4 mRNA. Our microarray dataset revealed that EFNA4 mRNA expression was associated with expression of NANOG and OCT4 mRNA, and OSCC patients showing high co-expression of EFNA4 with NANOG or OCT4 mRNA demonstrated poor recurrence-free survival rates. Targeting forward signaling of the EFNA4-EPHA10 axis may be a promising therapeutic approach for oral malignancies, and the combination of EFNA4 mRNA and downstream gene expression may be a useful prognostic biomarker for OSCC.Yu-Lin ChenYi-Chen YenChuan-Wei JangSsu-Han WangHsin-Ting HuangChung-Hsing ChenJenn-Ren HsiaoJang-Yang ChangYa-Wen ChenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yu-Lin Chen Yi-Chen Yen Chuan-Wei Jang Ssu-Han Wang Hsin-Ting Huang Chung-Hsing Chen Jenn-Ren Hsiao Jang-Yang Chang Ya-Wen Chen Ephrin A4-ephrin receptor A10 signaling promotes cell migration and spheroid formation by upregulating NANOG expression in oral squamous cell carcinoma cells
description	Abstract Ephrin type-A receptor 10 (EPHA10) has been implicated as a potential target for breast and prostate cancer therapy. However, its involvement in oral squamous cell carcinoma (OSCC) remains unclear. We demonstrated that EPHA10 supports in vivo tumor growth and lymphatic metastasis of OSCC cells. OSCC cell migration, epithelial mesenchymal transition (EMT), and sphere formation were found to be regulated by EPHA10, and EPHA10 was found to drive expression of some EMT- and stemness-associated transcription factors. Among EPHA10 ligands, exogenous ephrin A4 (EFNA4) induced the most OSCC cell migration and sphere formation, as well as up-regulation of SNAIL, NANOG, and OCT4. These effects were abolished by extracellular signal-regulated kinase (ERK) inhibition and NANOG knockdown. Also, EPHA10 was required for EFNA4-induced cell migration, sphere formation, and expression of NANOG and OCT4 mRNA. Our microarray dataset revealed that EFNA4 mRNA expression was associated with expression of NANOG and OCT4 mRNA, and OSCC patients showing high co-expression of EFNA4 with NANOG or OCT4 mRNA demonstrated poor recurrence-free survival rates. Targeting forward signaling of the EFNA4-EPHA10 axis may be a promising therapeutic approach for oral malignancies, and the combination of EFNA4 mRNA and downstream gene expression may be a useful prognostic biomarker for OSCC.
format	article
author	Yu-Lin Chen Yi-Chen Yen Chuan-Wei Jang Ssu-Han Wang Hsin-Ting Huang Chung-Hsing Chen Jenn-Ren Hsiao Jang-Yang Chang Ya-Wen Chen
author_facet	Yu-Lin Chen Yi-Chen Yen Chuan-Wei Jang Ssu-Han Wang Hsin-Ting Huang Chung-Hsing Chen Jenn-Ren Hsiao Jang-Yang Chang Ya-Wen Chen
author_sort	Yu-Lin Chen
title	Ephrin A4-ephrin receptor A10 signaling promotes cell migration and spheroid formation by upregulating NANOG expression in oral squamous cell carcinoma cells
title_short	Ephrin A4-ephrin receptor A10 signaling promotes cell migration and spheroid formation by upregulating NANOG expression in oral squamous cell carcinoma cells
title_full	Ephrin A4-ephrin receptor A10 signaling promotes cell migration and spheroid formation by upregulating NANOG expression in oral squamous cell carcinoma cells
title_fullStr	Ephrin A4-ephrin receptor A10 signaling promotes cell migration and spheroid formation by upregulating NANOG expression in oral squamous cell carcinoma cells
title_full_unstemmed	Ephrin A4-ephrin receptor A10 signaling promotes cell migration and spheroid formation by upregulating NANOG expression in oral squamous cell carcinoma cells
title_sort	ephrin a4-ephrin receptor a10 signaling promotes cell migration and spheroid formation by upregulating nanog expression in oral squamous cell carcinoma cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/21cf012a84ff48269dd235e08c02781b
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Ephrin A4-ephrin receptor A10 signaling promotes cell migration and spheroid formation by upregulating NANOG expression in oral squamous cell carcinoma cells

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