Loss of sphingosine kinase 1 increases lung metastases in the MMTV-PyMT mouse model of breast cancer
Name:
journal.pone.0252311.pdf
Size:
2.003Mb
Format:
PDF
Description:
Final Published Version
Affiliation
Department of Nutritional Sciences, College of Agriculture and Life Sciences, University of ArizonaIssue Date
2021
Metadata
Show full item recordPublisher
Public Library of ScienceCitation
Velazquez, F. N., Zhang, L., Viscardi, V., Trocchia, C., Hannun, Y. A., Obeid, L. M., & Snider, A. J. (2021). Loss of sphingosine kinase 1 increases lung metastases in the MMTV-PyMT mouse model of breast cancer. PLoS ONE, 16(5 May).Journal
PLoS ONERights
Copyright © 2021 Velazquez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License.Collection Information
This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.Abstract
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. Copyright: © 2021 Velazquez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Note
Open access journalISSN
1932-6203Version
Final published versionae974a485f413a2113503eed53cd6c53
10.1371/journal.pone.0252311
Scopus Count
Collections
Except where otherwise noted, this item's license is described as Copyright © 2021 Velazquez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License.