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Human ribonuclease 1 serves as a secretory ligand of ephrin A4 receptor and induces breast tumor initiation

Human ribonuclease 1 (hRNase 1) is critical to extracellular RNA clearance and innate immunity to achieve homeostasis and host defense; however, whether it plays a role in cancer remains elusive. Here, we demonstrate that hRNase 1, independently of its ribonucleolytic activity, enriches the stem-lik...

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Autores principales: Lee, Heng-Huan, Wang, Ying-Nai, Yang, Wen-Hao, Xia, Weiya, Wei, Yongkun, Chan, Li-Chuan, Wang, Yu-Han, Jiang, Zhou, Xu, Shouping, Yao, Jun, Qiu, Yufan, Hsu, Yi-Hsin, Hwang, Wei-Lun, Yan, Meisi, Cha, Jong-Ho, Hsu, Jennifer L., Shen, Jia, Ye, Yuanqing, Wu, Xifeng, Hou, Ming-Feng, Tseng, Lin-Ming, Wang, Shao-Chun, Pan, Mei-Ren, Yang, Chin-Hua, Wang, Yuan-Liang, Yamaguchi, Hirohito, Pang, Da, Hortobagyi, Gabriel N., Yu, Dihua, Hung, Mien-Chie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119676/
https://www.ncbi.nlm.nih.gov/pubmed/33986289
http://dx.doi.org/10.1038/s41467-021-23075-2
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author Lee, Heng-Huan
Wang, Ying-Nai
Yang, Wen-Hao
Xia, Weiya
Wei, Yongkun
Chan, Li-Chuan
Wang, Yu-Han
Jiang, Zhou
Xu, Shouping
Yao, Jun
Qiu, Yufan
Hsu, Yi-Hsin
Hwang, Wei-Lun
Yan, Meisi
Cha, Jong-Ho
Hsu, Jennifer L.
Shen, Jia
Ye, Yuanqing
Wu, Xifeng
Hou, Ming-Feng
Tseng, Lin-Ming
Wang, Shao-Chun
Pan, Mei-Ren
Yang, Chin-Hua
Wang, Yuan-Liang
Yamaguchi, Hirohito
Pang, Da
Hortobagyi, Gabriel N.
Yu, Dihua
Hung, Mien-Chie
author_facet Lee, Heng-Huan
Wang, Ying-Nai
Yang, Wen-Hao
Xia, Weiya
Wei, Yongkun
Chan, Li-Chuan
Wang, Yu-Han
Jiang, Zhou
Xu, Shouping
Yao, Jun
Qiu, Yufan
Hsu, Yi-Hsin
Hwang, Wei-Lun
Yan, Meisi
Cha, Jong-Ho
Hsu, Jennifer L.
Shen, Jia
Ye, Yuanqing
Wu, Xifeng
Hou, Ming-Feng
Tseng, Lin-Ming
Wang, Shao-Chun
Pan, Mei-Ren
Yang, Chin-Hua
Wang, Yuan-Liang
Yamaguchi, Hirohito
Pang, Da
Hortobagyi, Gabriel N.
Yu, Dihua
Hung, Mien-Chie
author_sort Lee, Heng-Huan
collection PubMed
description Human ribonuclease 1 (hRNase 1) is critical to extracellular RNA clearance and innate immunity to achieve homeostasis and host defense; however, whether it plays a role in cancer remains elusive. Here, we demonstrate that hRNase 1, independently of its ribonucleolytic activity, enriches the stem-like cell population and enhances the tumor-initiating ability of breast cancer cells. Specifically, secretory hRNase 1 binds to and activates the tyrosine kinase receptor ephrin A4 (EphA4) signaling to promote breast tumor initiation in an autocrine/paracrine manner, which is distinct from the classical EphA4-ephrin juxtacrine signaling through contact-dependent cell-cell communication. In addition, analysis of human breast tumor tissue microarrays reveals a positive correlation between hRNase 1, EphA4 activation, and stem cell marker CD133. Notably, high hRNase 1 level in plasma samples is positively associated with EphA4 activation in tumor tissues from breast cancer patients, highlighting the pathological relevance of the hRNase 1-EphA4 axis in breast cancer. The discovery of hRNase 1 as a secretory ligand of EphA4 that enhances breast cancer stemness suggests a potential treatment strategy by inactivating the hRNase 1-EphA4 axis.
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spelling pubmed-81196762021-05-18 Human ribonuclease 1 serves as a secretory ligand of ephrin A4 receptor and induces breast tumor initiation Lee, Heng-Huan Wang, Ying-Nai Yang, Wen-Hao Xia, Weiya Wei, Yongkun Chan, Li-Chuan Wang, Yu-Han Jiang, Zhou Xu, Shouping Yao, Jun Qiu, Yufan Hsu, Yi-Hsin Hwang, Wei-Lun Yan, Meisi Cha, Jong-Ho Hsu, Jennifer L. Shen, Jia Ye, Yuanqing Wu, Xifeng Hou, Ming-Feng Tseng, Lin-Ming Wang, Shao-Chun Pan, Mei-Ren Yang, Chin-Hua Wang, Yuan-Liang Yamaguchi, Hirohito Pang, Da Hortobagyi, Gabriel N. Yu, Dihua Hung, Mien-Chie Nat Commun Article Human ribonuclease 1 (hRNase 1) is critical to extracellular RNA clearance and innate immunity to achieve homeostasis and host defense; however, whether it plays a role in cancer remains elusive. Here, we demonstrate that hRNase 1, independently of its ribonucleolytic activity, enriches the stem-like cell population and enhances the tumor-initiating ability of breast cancer cells. Specifically, secretory hRNase 1 binds to and activates the tyrosine kinase receptor ephrin A4 (EphA4) signaling to promote breast tumor initiation in an autocrine/paracrine manner, which is distinct from the classical EphA4-ephrin juxtacrine signaling through contact-dependent cell-cell communication. In addition, analysis of human breast tumor tissue microarrays reveals a positive correlation between hRNase 1, EphA4 activation, and stem cell marker CD133. Notably, high hRNase 1 level in plasma samples is positively associated with EphA4 activation in tumor tissues from breast cancer patients, highlighting the pathological relevance of the hRNase 1-EphA4 axis in breast cancer. The discovery of hRNase 1 as a secretory ligand of EphA4 that enhances breast cancer stemness suggests a potential treatment strategy by inactivating the hRNase 1-EphA4 axis. Nature Publishing Group UK 2021-05-13 /pmc/articles/PMC8119676/ /pubmed/33986289 http://dx.doi.org/10.1038/s41467-021-23075-2 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Lee, Heng-Huan
Wang, Ying-Nai
Yang, Wen-Hao
Xia, Weiya
Wei, Yongkun
Chan, Li-Chuan
Wang, Yu-Han
Jiang, Zhou
Xu, Shouping
Yao, Jun
Qiu, Yufan
Hsu, Yi-Hsin
Hwang, Wei-Lun
Yan, Meisi
Cha, Jong-Ho
Hsu, Jennifer L.
Shen, Jia
Ye, Yuanqing
Wu, Xifeng
Hou, Ming-Feng
Tseng, Lin-Ming
Wang, Shao-Chun
Pan, Mei-Ren
Yang, Chin-Hua
Wang, Yuan-Liang
Yamaguchi, Hirohito
Pang, Da
Hortobagyi, Gabriel N.
Yu, Dihua
Hung, Mien-Chie
Human ribonuclease 1 serves as a secretory ligand of ephrin A4 receptor and induces breast tumor initiation
title Human ribonuclease 1 serves as a secretory ligand of ephrin A4 receptor and induces breast tumor initiation
title_full Human ribonuclease 1 serves as a secretory ligand of ephrin A4 receptor and induces breast tumor initiation
title_fullStr Human ribonuclease 1 serves as a secretory ligand of ephrin A4 receptor and induces breast tumor initiation
title_full_unstemmed Human ribonuclease 1 serves as a secretory ligand of ephrin A4 receptor and induces breast tumor initiation
title_short Human ribonuclease 1 serves as a secretory ligand of ephrin A4 receptor and induces breast tumor initiation
title_sort human ribonuclease 1 serves as a secretory ligand of ephrin a4 receptor and induces breast tumor initiation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119676/
https://www.ncbi.nlm.nih.gov/pubmed/33986289
http://dx.doi.org/10.1038/s41467-021-23075-2
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