Logo Medical Science Monitor

Call: +1.631.470.9640
Mon - Fri 10:00 am - 02:00 pm EST

Contact Us

Logo Medical Science Monitor Logo Medical Science Monitor Logo Medical Science Monitor

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 Zhang1AEFG

DOI: 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: Neoplasm Metastasis, Receptors, Lysosphingolipid, Triple Negative Breast Neoplasms

0 Comments

Editorial

01 January 2022 : Editorial  

Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Patients

Dinah V. Parums
Science Editor, Medical Science Monitor, International Scientific Information, Inc., Melville, NY, USA

DOI: 10.12659/MSM.935952

Med Sci Monit 2022; 28:e935952

SARS-CoV-2/COVID-19

11 January 2022 : Clinical Research  

A 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 Analysis  

Virtual 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 Research  

A Prospective Observational Study of 42 Patients with COVID-19 infection and a History of Hepatitis C Virus...

Med Sci Monit 2021; 27:e935075

30 December 2021 : Clinical Research  

Retrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...

Med Sci Monit 2021; 27:e935379

In Press

14 Jan 2022 : Database Analysis  

Identification of Key Genes Associated with Brain Metastasis from Breast Cancer: A Bioinformatics Analysis

Med Sci Monit In Press; DOI: 10.12659/MSM.935071  

13 Jan 2022 : Review article  

A Review of Current Clinical Concepts in the Pathophysiology, Etiology, Diagnosis, and Management of Hyperc...

Med Sci Monit In Press; DOI: 10.12659/MSM.935821  

13 Jan 2022 : Clinical Research  

Effect of Cerebral Microbleeds on Cognitive Function and Quality of Life in Parkinson Disease

Med Sci Monit In Press; DOI: 10.12659/MSM.935026  

11 Jan 2022 : Clinical Research  

A 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  

Most Viewed Current Articles

30 Dec 2021 : Clinical Research  

Retrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...

DOI :10.12659/MSM.935379

Med Sci Monit 2021; 27:e935379

01 Nov 2020 : Review article  

Long-Term Respiratory and Neurological Sequelae of COVID-19

DOI :10.12659/MSM.928996

Med Sci Monit 2020; 26:e928996

05 Mar 2020 : Clinical Research  

The Effects of Social Support on Sleep Quality of Medical Staff Treating Patients with Coronavirus Disease ...

DOI :10.12659/MSM.923549

Med Sci Monit 2020; 26:e923549

15 Apr 2020 : Clinical Research  

Psychological Impact and Coping Strategies of Frontline Medical Staff in Hunan Between January and March 20...

DOI :10.12659/MSM.924171

Med Sci Monit 2020; 26:e924171

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750