Loss of sphingosine kinase 1 increases lung metastases in the MMTV-PyMT mouse model of breast cancer.

Breast cancer is a very heterogeneous disease, and ~30% of breast cancer patients succumb to metastasis, highlighting the need to understand the mechanisms of breast cancer progression in order to identify new molecular targets for treatment. Sphingosine kinase 1 (SK1) has been shown to be upregulat...

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Autores principales:	Fabiola N Velazquez, Leiqing Zhang, Valentina Viscardi, Carolena Trocchia, Yusuf A Hannun, Lina M Obeid, Ashley J Snider
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/82365634bb0c4285b6c0179117fab065
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spelling	oai:doaj.org-article:82365634bb0c4285b6c0179117fab0652021-11-25T06:23:40ZLoss of sphingosine kinase 1 increases lung metastases in the MMTV-PyMT mouse model of breast cancer.1932-620310.1371/journal.pone.0252311https://doaj.org/article/82365634bb0c4285b6c0179117fab0652021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0252311https://doaj.org/toc/1932-6203Breast cancer is a very heterogeneous disease, and ~30% of breast cancer patients succumb to metastasis, highlighting the need to understand the mechanisms of breast cancer progression in order to identify new molecular targets for treatment. Sphingosine kinase 1 (SK1) has been shown to be upregulated in patients with breast cancer, and several studies have suggested its involvement in breast cancer progression and/or metastasis, mostly based on cell studies. In this work we evaluated the role of SK1 in breast cancer development and metastasis using a transgenic breast cancer model, mouse mammary tumor virus-polyoma middle tumor-antigen (MMTV-PyMT), that closely resembles the characteristics and evolution of human breast cancer. The results show that SK1 deficiency does not alter tumor latency or growth, but significantly increases the number of metastatic lung nodules and the average metastasis size in the lung of MMTV-PyMT mice. Additionally, analysis of Kaplan-Meier plotter of human disease shows that high SK1 mRNA expression can be associated with a better prognosis for breast cancer patients. These results suggest a metastasis-suppressing function for SK1 in the MMTV-PyMT model of breast cancer, and that its role in regulating human breast cancer progression and metastasis may be dependent on the breast cancer type.Fabiola N VelazquezLeiqing ZhangValentina ViscardiCarolena TrocchiaYusuf A HannunLina M ObeidAshley J SniderPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 5, p e0252311 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Fabiola N Velazquez Leiqing Zhang Valentina Viscardi Carolena Trocchia Yusuf A Hannun Lina M Obeid Ashley J Snider Loss of sphingosine kinase 1 increases lung metastases in the MMTV-PyMT mouse model of breast cancer.
description	Breast cancer is a very heterogeneous disease, and ~30% of breast cancer patients succumb to metastasis, highlighting the need to understand the mechanisms of breast cancer progression in order to identify new molecular targets for treatment. Sphingosine kinase 1 (SK1) has been shown to be upregulated in patients with breast cancer, and several studies have suggested its involvement in breast cancer progression and/or metastasis, mostly based on cell studies. In this work we evaluated the role of SK1 in breast cancer development and metastasis using a transgenic breast cancer model, mouse mammary tumor virus-polyoma middle tumor-antigen (MMTV-PyMT), that closely resembles the characteristics and evolution of human breast cancer. The results show that SK1 deficiency does not alter tumor latency or growth, but significantly increases the number of metastatic lung nodules and the average metastasis size in the lung of MMTV-PyMT mice. Additionally, analysis of Kaplan-Meier plotter of human disease shows that high SK1 mRNA expression can be associated with a better prognosis for breast cancer patients. These results suggest a metastasis-suppressing function for SK1 in the MMTV-PyMT model of breast cancer, and that its role in regulating human breast cancer progression and metastasis may be dependent on the breast cancer type.
format	article
author	Fabiola N Velazquez Leiqing Zhang Valentina Viscardi Carolena Trocchia Yusuf A Hannun Lina M Obeid Ashley J Snider
author_facet	Fabiola N Velazquez Leiqing Zhang Valentina Viscardi Carolena Trocchia Yusuf A Hannun Lina M Obeid Ashley J Snider
author_sort	Fabiola N Velazquez
title	Loss of sphingosine kinase 1 increases lung metastases in the MMTV-PyMT mouse model of breast cancer.
title_short	Loss of sphingosine kinase 1 increases lung metastases in the MMTV-PyMT mouse model of breast cancer.
title_full	Loss of sphingosine kinase 1 increases lung metastases in the MMTV-PyMT mouse model of breast cancer.
title_fullStr	Loss of sphingosine kinase 1 increases lung metastases in the MMTV-PyMT mouse model of breast cancer.
title_full_unstemmed	Loss of sphingosine kinase 1 increases lung metastases in the MMTV-PyMT mouse model of breast cancer.
title_sort	loss of sphingosine kinase 1 increases lung metastases in the mmtv-pymt mouse model of breast cancer.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/82365634bb0c4285b6c0179117fab065
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Loss of sphingosine kinase 1 increases lung metastases in the MMTV-PyMT mouse model of breast cancer.

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