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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| creator | Velazquez, Fabiola N Zhang, Leiqing Viscardi, Valentina Trocchia, Carolena Hannun, Yusuf A Obeid, Lina M Snider, Ashley J |
| 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. |
| doi_str_mv | 10.1371/journal.pone.0252311 |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0252311</identifier><identifier>PMID: 34043703</identifier><language>eng</language><publisher>San Francisco: Public Library of Science</publisher><subject>Agriculture ; Antigens ; Biology and Life Sciences ; Breast cancer ; Cancer therapies ; Cell adhesion & migration ; Chemotherapy ; Complications and side effects ; Editing ; Engineering and Technology ; Enzymes ; Epidermal growth factor ; ErbB-2 protein ; Estrogen receptors ; Estrogens ; Funding ; Gene expression ; Growth factors ; Kinases ; Laboratories ; Lung cancer ; Lungs ; Medical prognosis ; Medicine ; Medicine and Health Sciences ; Metastases ; Metastasis ; Phosphotransferases ; Physiological aspects ; Progesterone ; Quality of life ; Receptors ; Research and Analysis Methods ; Reviews ; Risk factors ; Sphingosine ; Sphingosine kinase ; Target recognition ; Therapeutic targets ; Tumors ; Viruses</subject><ispartof>PloS one, 2021-05, Vol.16 (5), p.e0252311-e0252311</ispartof><rights>COPYRIGHT 2021 Public Library of Science</rights><rights>2021 Velazquez et al. 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Tiffany</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Loss of sphingosine kinase 1 increases lung metastases in the MMTV-PyMT mouse model of breast cancer</atitle><jtitle>PloS one</jtitle><date>2021-05-27</date><risdate>2021</risdate><volume>16</volume><issue>5</issue><spage>e0252311</spage><epage>e0252311</epage><pages>e0252311-e0252311</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><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. 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| subjects | Agriculture Antigens Biology and Life Sciences Breast cancer Cancer therapies Cell adhesion & migration Chemotherapy Complications and side effects Editing Engineering and Technology Enzymes Epidermal growth factor ErbB-2 protein Estrogen receptors Estrogens Funding Gene expression Growth factors Kinases Laboratories Lung cancer Lungs Medical prognosis Medicine Medicine and Health Sciences Metastases Metastasis Phosphotransferases Physiological aspects Progesterone Quality of life Receptors Research and Analysis Methods Reviews Risk factors Sphingosine Sphingosine kinase Target recognition Therapeutic targets Tumors Viruses |
| title | Loss of sphingosine kinase 1 increases lung metastases in the MMTV-PyMT mouse model of breast cancer |
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