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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: Velazquez, Fabiola N., Zhang, Leiqing, Viscardi, Valentina, Trocchia, Carolena, Hannun, Yusuf A., Obeid, Lina M., Snider, Ashley J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158862/
https://www.ncbi.nlm.nih.gov/pubmed/34043703
http://dx.doi.org/10.1371/journal.pone.0252311
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author Velazquez, Fabiola N.
Zhang, Leiqing
Viscardi, Valentina
Trocchia, Carolena
Hannun, Yusuf A.
Obeid, Lina M.
Snider, Ashley J.
author_facet Velazquez, Fabiola N.
Zhang, Leiqing
Viscardi, Valentina
Trocchia, Carolena
Hannun, Yusuf A.
Obeid, Lina M.
Snider, Ashley J.
author_sort Velazquez, Fabiola N.
collection PubMed
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.
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spelling pubmed-81588622021-06-09 Loss of sphingosine kinase 1 increases lung metastases in the MMTV-PyMT mouse model of breast cancer Velazquez, Fabiola N. Zhang, Leiqing Viscardi, Valentina Trocchia, Carolena Hannun, Yusuf A. Obeid, Lina M. Snider, Ashley J. PLoS One Research Article 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. Public Library of Science 2021-05-27 /pmc/articles/PMC8158862/ /pubmed/34043703 http://dx.doi.org/10.1371/journal.pone.0252311 Text en © 2021 Velazquez et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Velazquez, Fabiola N.
Zhang, Leiqing
Viscardi, Valentina
Trocchia, Carolena
Hannun, Yusuf A.
Obeid, Lina M.
Snider, Ashley J.
Loss of sphingosine kinase 1 increases lung metastases in the MMTV-PyMT mouse model of breast cancer
title 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_short 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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158862/
https://www.ncbi.nlm.nih.gov/pubmed/34043703
http://dx.doi.org/10.1371/journal.pone.0252311
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