01 April 2018 : Laboratory Research
Triple Negative Breast Cancer Depends on Sphingosine Kinase 1 (SphK1)/Sphingosine-1-Phosphate (S1P)/Sphingosine 1-Phosphate Receptor 3 (S1PR3)/Notch Signaling for MetastasisShushu Wang1ABCDEF*, Yueyang Liang1BC, Wenxiao Chang2BC, Baoquan Hu1ABC, Yi Zhang1AEFG
Med Sci Monit 2018; 24: LBR1912-1923
BACKGROUND: Triple negative breast cancer (TNBC) has a more aggressive recurrence. Previous reports have demonstrated that sphingosine kinase 1 (SphK1) is a crucial regulator of breast cancer progression. However, the correlation of SphK1 with clinical prognosis has been poorly investigated. Thus, we aimed to elaborate the role of SphK1 in TNBC metastasis.
MATERIAL AND METHODS: We first determined the level of SphK1 in breast cancer tissue samples and breast cancer cells. Furthermore, the expression of HER2 and phosphor-SphK1 (pSphK1) in human breast cancer tissue samples was determined by immunohistochemical analysis. Associations between SphK1 and clinical parameters of tumors were analyzed. The activity of SphK1 was measured by fluorescence analysis. Extracellular sphingosine-1-phosphate (S1P) was detected using an ELISA kit. Associations between SphK1 and metastasis potential were analyzed by Transwell assay.
RESULTS: Levels of SphK1 in TNBC patients were significantly higher than levels in other patients with other breast tumors. The expression of SphK1 was positively correlated with poor overall survival (OS) and progression-free survival (PFS), as well as poor response to 5-FU and doxorubicin. The depression of SphK1 thus could repress the Notch signaling pathway, reduce migration, and invasion of TNBC cells in vivo and in vitro. Furthermore, silencing of SphK1 by Ad-SPHK1-siRNA or SphK1 inhibitor PF543 sensitized TNBCs to 5-FU and doxorubicin. Our results also indicated that SphK1 inhibition could effectively counteracts tumors metastasis via Notch signaling pathways, indicating a potentially anti-tumor strategy in TNBC.
CONCLUSIONS: We found that elevated levels of pSphK1 were positive correlation with high expression of S1P, which in turn promoted metastasis of TNBC through S1P/S1PR3/Notch signaling pathway.
Keywords: Neoplasm Metastasis, Receptors, Lysosphingolipid, Triple Negative Breast Neoplasms
01 January 2022 : EditorialEditorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Patients
Med Sci Monit 2022; 28:e935952
11 January 2022 : Clinical ResearchA Remote Questionnaire-Based Study to Compare Alcohol Use in 1030 Final-Year High School Students in Split-...
Med Sci Monit In Press; DOI: 10.12659/MSM.935567
08 November 2021 : Database AnalysisVirtual Screening and Molecular Docking to Study the Mechanism of Chinese Medicines in the Treatment of Cor...
Med Sci Monit In Press; DOI: 10.12659/MSM.934102
31 December 2021 : Clinical ResearchA Prospective Observational Study of 42 Patients with COVID-19 infection and a History of Hepatitis C Virus...
Med Sci Monit 2021; 27:e935075
19 Jan 2022 : Clinical ResearchA Retrospective Study to Compare the Effects of Methylprednisolone and Dexamethasone in 35 Patients with An...
Med Sci Monit In Press; DOI: 10.12659/MSM.934703
17 Jan 2022 : Clinical ResearchUnveiling the Differences in Biological Properties of Dental Pulp Stem Cells from Normal and Inflamed Pulp:...
Med Sci Monit In Press; DOI: 10.12659/MSM.934511
14 Jan 2022 : Database AnalysisIdentification of Key Genes Associated with Brain Metastasis from Breast Cancer: A Bioinformatics Analysis
Med Sci Monit In Press; DOI: 10.12659/MSM.935071
Most Viewed Current Articles
30 Dec 2021 : Clinical ResearchRetrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...
Med Sci Monit 2021; 27:e935379
01 Nov 2020 : Review articleLong-Term Respiratory and Neurological Sequelae of COVID-19
Med Sci Monit 2020; 26:e928996
05 Mar 2020 : Clinical ResearchThe Effects of Social Support on Sleep Quality of Medical Staff Treating Patients with Coronavirus Disease ...
Med Sci Monit 2020; 26:e923549