Loss of sphingosine kinase 1 increases lung metastases in the MMTV-PyMT mouse model of breast cancer.
Animals
Carcinogenesis
Disease Models, Animal
Female
Gene Expression Regulation, Neoplastic
Lung Neoplasms
/ secondary
Mammary Neoplasms, Experimental
/ metabolism
Mice
Mice, Knockout
Phosphotransferases (Alcohol Group Acceptor)
/ physiology
Retroviridae Infections
/ metabolism
Tumor Virus Infections
/ metabolism
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2021
2021
Historique:
received:
08
01
2021
accepted:
13
05
2021
entrez:
27
5
2021
pubmed:
28
5
2021
medline:
25
2
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34043703
doi: 10.1371/journal.pone.0252311
pii: PONE-D-20-40282
pmc: PMC8158862
doi:
Substances chimiques
Phosphotransferases (Alcohol Group Acceptor)
EC 2.7.1.-
Sphk1 protein, mouse
EC 2.7.1.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0252311Subventions
Organisme : NCI NIH HHS
ID : P01 CA097132
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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