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 Metastasis
Shushu Wang1ABCDEF*, Yueyang Liang1BC, Wenxiao Chang2BC, Baoquan Hu1ABC, Yi Zhang1AEFGDOI: 10.12659/MSM.905833
Med Sci Monit 2018; 24: LBR1912-1923
Abstract
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: Receptors, Lysosphingolipid, Triple Negative Breast Neoplasms
Editorial
01 May 2024 : Editorial
Editorial: First Regulatory Approval for Adoptive Cell Therapy with Autologous Tumor-Infiltrating Lymphocytes (TILs) – Lifileucel (Amtagvi)DOI: 10.12659/MSM.944927
Med Sci Monit 2024; 30:e944927
In Press
14 Mar 2024 : Clinical Research
Renal Dysfunction Increases Risk of Adverse Cardiovascular Events in 5-Year Follow-Up Study of Intermediate...Med Sci Monit In Press; DOI: 10.12659/MSM.943956
15 Mar 2024 : Clinical Research
Impact of One-Lung Ventilation on Oxygenation and Ventilation Time in Thoracoscopic Heart Surgery: A Compar...Med Sci Monit In Press; DOI: 10.12659/MSM.943089
14 Mar 2024 : Clinical Research
Differential DHA and EPA Levels in Women with Preterm and Term Births: A Tertiary Hospital Study in IndonesiaMed Sci Monit In Press; DOI: 10.12659/MSM.943895
15 Mar 2024 : Clinical Research
Evaluation of an Optimized Workflow for the Radiofrequency Catheter Ablation of Paroxysmal Atrial FibrillationMed Sci Monit In Press; DOI: 10.12659/MSM.943526
Most Viewed Current Articles
17 Jan 2024 : Review article
Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron VariantDOI :10.12659/MSM.942799
Med Sci Monit 2024; 30:e942799
14 Dec 2022 : Clinical Research
Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase LevelsDOI :10.12659/MSM.937990
Med Sci Monit 2022; 28:e937990
16 May 2023 : Clinical Research
Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...DOI :10.12659/MSM.940387
Med Sci Monit 2023; 29:e940387
01 Jan 2022 : Editorial
Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...DOI :10.12659/MSM.935952
Med Sci Monit 2022; 28:e935952