Musashi-1 promotes a cancer stem cell lineage and chemoresistance in colorectal cancer cells

Abstract Colorectal cancers (CRCs) are a critical health issue worldwide. Cancer stem cell (CSC) lineages are associated with tumour transformation, progression, and malignant transformation. However, how lineages are transformed and how chemoresistance is acquired by CRCs remain largely unknown. In...

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Autores principales:	Guang-Yuh Chiou, Tzu-Wei Yang, Chi-Chou Huang, Chia-Ying Tang, Jung-Yi Yen, Ming-Chang Tsai, Hsuan-Yi Chen, Nurul Fadhilah, Chun-Che Lin, Yuh-Jyh Jong
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9652c4570e784a85a11deae6b9762d4f
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spelling	oai:doaj.org-article:9652c4570e784a85a11deae6b9762d4f2021-12-02T15:04:54ZMusashi-1 promotes a cancer stem cell lineage and chemoresistance in colorectal cancer cells10.1038/s41598-017-02057-92045-2322https://doaj.org/article/9652c4570e784a85a11deae6b9762d4f2017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02057-9https://doaj.org/toc/2045-2322Abstract Colorectal cancers (CRCs) are a critical health issue worldwide. Cancer stem cell (CSC) lineages are associated with tumour transformation, progression, and malignant transformation. However, how lineages are transformed and how chemoresistance is acquired by CRCs remain largely unknown. In this report, we demonstrated that the RNA-binding protein Musashi-1 enhanced the development of CD44+ colorectal CSCs and triggered the formation of anti-apoptotic stress granules (SGs). Our results indicated that CD44+ CSC lineage-specific induction of tumour malignancies was controlled by Musashi-1. In addition, Musashi-1 formed SGs when CRC cell lines were treated with 5-fluorouracil. The C-terminal domain of Musashi-1 was critical for recruitment of Musashi-1 into SGs. Intracellular Musashi-1 SGs enhanced the chemoresistance of CRCs. Analysis of clinical CRC samples indicated that Musashi-1 expression was prominent in CRC stage IIA and IIB. In summary, we demonstrated that Musashi-1, a stemness gene, is a critical modulator that promotes the development of CD44+ colorectal CSCs and also enhances CRC chemoresistance via formation of SGs. Our findings elucidated a novel mechanism of CRC chemoresistance through increased anti-apoptotic effects via Musashi-1-associated SGs.Guang-Yuh ChiouTzu-Wei YangChi-Chou HuangChia-Ying TangJung-Yi YenMing-Chang TsaiHsuan-Yi ChenNurul FadhilahChun-Che LinYuh-Jyh JongNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Guang-Yuh Chiou Tzu-Wei Yang Chi-Chou Huang Chia-Ying Tang Jung-Yi Yen Ming-Chang Tsai Hsuan-Yi Chen Nurul Fadhilah Chun-Che Lin Yuh-Jyh Jong Musashi-1 promotes a cancer stem cell lineage and chemoresistance in colorectal cancer cells
description	Abstract Colorectal cancers (CRCs) are a critical health issue worldwide. Cancer stem cell (CSC) lineages are associated with tumour transformation, progression, and malignant transformation. However, how lineages are transformed and how chemoresistance is acquired by CRCs remain largely unknown. In this report, we demonstrated that the RNA-binding protein Musashi-1 enhanced the development of CD44+ colorectal CSCs and triggered the formation of anti-apoptotic stress granules (SGs). Our results indicated that CD44+ CSC lineage-specific induction of tumour malignancies was controlled by Musashi-1. In addition, Musashi-1 formed SGs when CRC cell lines were treated with 5-fluorouracil. The C-terminal domain of Musashi-1 was critical for recruitment of Musashi-1 into SGs. Intracellular Musashi-1 SGs enhanced the chemoresistance of CRCs. Analysis of clinical CRC samples indicated that Musashi-1 expression was prominent in CRC stage IIA and IIB. In summary, we demonstrated that Musashi-1, a stemness gene, is a critical modulator that promotes the development of CD44+ colorectal CSCs and also enhances CRC chemoresistance via formation of SGs. Our findings elucidated a novel mechanism of CRC chemoresistance through increased anti-apoptotic effects via Musashi-1-associated SGs.
format	article
author	Guang-Yuh Chiou Tzu-Wei Yang Chi-Chou Huang Chia-Ying Tang Jung-Yi Yen Ming-Chang Tsai Hsuan-Yi Chen Nurul Fadhilah Chun-Che Lin Yuh-Jyh Jong
author_facet	Guang-Yuh Chiou Tzu-Wei Yang Chi-Chou Huang Chia-Ying Tang Jung-Yi Yen Ming-Chang Tsai Hsuan-Yi Chen Nurul Fadhilah Chun-Che Lin Yuh-Jyh Jong
author_sort	Guang-Yuh Chiou
title	Musashi-1 promotes a cancer stem cell lineage and chemoresistance in colorectal cancer cells
title_short	Musashi-1 promotes a cancer stem cell lineage and chemoresistance in colorectal cancer cells
title_full	Musashi-1 promotes a cancer stem cell lineage and chemoresistance in colorectal cancer cells
title_fullStr	Musashi-1 promotes a cancer stem cell lineage and chemoresistance in colorectal cancer cells
title_full_unstemmed	Musashi-1 promotes a cancer stem cell lineage and chemoresistance in colorectal cancer cells
title_sort	musashi-1 promotes a cancer stem cell lineage and chemoresistance in colorectal cancer cells
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/9652c4570e784a85a11deae6b9762d4f
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_version_	1718389030358351872

Musashi-1 promotes a cancer stem cell lineage and chemoresistance in colorectal cancer cells

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