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S1PR1 regulates the switch of two angiogenic modes by VE-cadherin phosphorylation in breast cancer

Angiogenesis in solid tumors is divided into two modes: endothelium-dependent vessel (EDV) and vasculogenic mimicry (VM). Sphingosine-1-phosphate receptor 1 (S1PR1) plays a vital role on EDV in a variety of human tumors. However, the relationship between S1PR1 and VM is not clear. The aim of this st...

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Autores principales: Liu, Shuang, Ni, Chunsheng, Zhang, Danfang, Sun, Huizhi, Dong, Xueyi, Che, Na, Liang, Xiaohui, Chen, Chen, Liu, Fang, Bai, Jingru, Lin, Xian, Zhao, Xiulan, Sun, Baocun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6393557/
https://www.ncbi.nlm.nih.gov/pubmed/30814488
http://dx.doi.org/10.1038/s41419-019-1411-x
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author Liu, Shuang
Ni, Chunsheng
Zhang, Danfang
Sun, Huizhi
Dong, Xueyi
Che, Na
Liang, Xiaohui
Chen, Chen
Liu, Fang
Bai, Jingru
Lin, Xian
Zhao, Xiulan
Sun, Baocun
author_facet Liu, Shuang
Ni, Chunsheng
Zhang, Danfang
Sun, Huizhi
Dong, Xueyi
Che, Na
Liang, Xiaohui
Chen, Chen
Liu, Fang
Bai, Jingru
Lin, Xian
Zhao, Xiulan
Sun, Baocun
author_sort Liu, Shuang
collection PubMed
description Angiogenesis in solid tumors is divided into two modes: endothelium-dependent vessel (EDV) and vasculogenic mimicry (VM). Sphingosine-1-phosphate receptor 1 (S1PR1) plays a vital role on EDV in a variety of human tumors. However, the relationship between S1PR1 and VM is not clear. The aim of this study is to investigate S1PR1 on the regulation of EDV and mimicry formation in breast cancer. Here we show that S1PR1 phosphorylates the complex of VE-cadherin to regulate the switch of EDV and mimicry formation. Suppression of S1PR1 impairs EDV, but contributes to the generation of VM, invasion, and metastasis in vivo and vitro. By inhibiting RhoA activation, the S1PR1/VE-cadherin signaling is blocked. S1PR1 controls VE-cadherin expression and EDV via RhoA activation. Moreover, the low expression of S1PR1 correlates with VM and poor prognosis in breast cancer patient. The results show that S1PR1 regulated RhoA activation to accelerate VE-cadherin phosphorylation (Y731), leading to increased EDV and reduced VM in breast cancer. S1PR1 may provide a new thinking direction for antiangiogenic therapy for patients with breast cancer.
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spelling pubmed-63935572019-02-28 S1PR1 regulates the switch of two angiogenic modes by VE-cadherin phosphorylation in breast cancer Liu, Shuang Ni, Chunsheng Zhang, Danfang Sun, Huizhi Dong, Xueyi Che, Na Liang, Xiaohui Chen, Chen Liu, Fang Bai, Jingru Lin, Xian Zhao, Xiulan Sun, Baocun Cell Death Dis Article Angiogenesis in solid tumors is divided into two modes: endothelium-dependent vessel (EDV) and vasculogenic mimicry (VM). Sphingosine-1-phosphate receptor 1 (S1PR1) plays a vital role on EDV in a variety of human tumors. However, the relationship between S1PR1 and VM is not clear. The aim of this study is to investigate S1PR1 on the regulation of EDV and mimicry formation in breast cancer. Here we show that S1PR1 phosphorylates the complex of VE-cadherin to regulate the switch of EDV and mimicry formation. Suppression of S1PR1 impairs EDV, but contributes to the generation of VM, invasion, and metastasis in vivo and vitro. By inhibiting RhoA activation, the S1PR1/VE-cadherin signaling is blocked. S1PR1 controls VE-cadherin expression and EDV via RhoA activation. Moreover, the low expression of S1PR1 correlates with VM and poor prognosis in breast cancer patient. The results show that S1PR1 regulated RhoA activation to accelerate VE-cadherin phosphorylation (Y731), leading to increased EDV and reduced VM in breast cancer. S1PR1 may provide a new thinking direction for antiangiogenic therapy for patients with breast cancer. Nature Publishing Group UK 2019-02-27 /pmc/articles/PMC6393557/ /pubmed/30814488 http://dx.doi.org/10.1038/s41419-019-1411-x Text en © The Author(s) 2019 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/.
spellingShingle Article
Liu, Shuang
Ni, Chunsheng
Zhang, Danfang
Sun, Huizhi
Dong, Xueyi
Che, Na
Liang, Xiaohui
Chen, Chen
Liu, Fang
Bai, Jingru
Lin, Xian
Zhao, Xiulan
Sun, Baocun
S1PR1 regulates the switch of two angiogenic modes by VE-cadherin phosphorylation in breast cancer
title S1PR1 regulates the switch of two angiogenic modes by VE-cadherin phosphorylation in breast cancer
title_full S1PR1 regulates the switch of two angiogenic modes by VE-cadherin phosphorylation in breast cancer
title_fullStr S1PR1 regulates the switch of two angiogenic modes by VE-cadherin phosphorylation in breast cancer
title_full_unstemmed S1PR1 regulates the switch of two angiogenic modes by VE-cadherin phosphorylation in breast cancer
title_short S1PR1 regulates the switch of two angiogenic modes by VE-cadherin phosphorylation in breast cancer
title_sort s1pr1 regulates the switch of two angiogenic modes by ve-cadherin phosphorylation in breast cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6393557/
https://www.ncbi.nlm.nih.gov/pubmed/30814488
http://dx.doi.org/10.1038/s41419-019-1411-x
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