Involvement of Sphingosine Kinases/Sphingosine-1-Phosphate (S1P)/S1P Receptors in Breast Cancer Subtypes

Abstract

There is emerging evidence suggesting sphingolipids as critical regulators of cancer development and progression. Sphingolipids are potent bioactive lipids involved in fundamental biological processes including cell proliferation, apoptosis, angiogenesis, senescence, stress response and transformation. Ceramide, sphingosine and Sphingosine-1-phosphate (S1P) are inter-convertible sphingolipids with opposing effects on cell fate. Furthermore, S1P either acts directly on intracellular targets or through G-protein coupled S1PRs (S1P1-5) to mediate their specific effects. This review will discuss the roles of key sphingolipids, sphingosine kinases (SphKs) and S1P receptors (S1PRs) in tumor growth and acquisition of resistance to chemotherapy in four subtypes of breast cancer that are categorized based on the status of hormone receptors and human epidermal growth factor 2 (HER2) receptors.