Sphk1 participates in malignant progression of breast cancer by regulating epithelial-mesenchymal transition and stem cell characteristics.

Sphingosine kinase 1 (Sphk1) is abnormally expressed in various tumors. This study explored the effects of Sphk1 in the polarity of breast cancer (BC) epithelial cells and on stem cell characteristics. Reverse transcription quantitative PCR (RT-qPCR) was performed to detect Sphk1 levels in human mammary epithelial cells (MCF-10A) and BC cell lines (MCF-7, T47D, SKBR3, MDA-MB-231, and BT-474). After Sphk1-overexpression or Sphk1 silencing, the morphology of cells and stem cell-like properties of BC cells were analyzed. Metastasis of BC cells was assessed by wound healing and Transwell assays. Western blotting was performed to detect levels of epithelial-mesenchymal transition (EMT)-related proteins (E-cadherin, N-cadherin and Vimentin) and stem cell-specific markers (SOX2, OCT4, NANOG and ALDH1). Sphk1 was increased in BC cell lines than MCF-10A. Sphk1 induced EMT, regulated expression of EMT-related proteins, and accelerated the migration and invasion of BC cells. Silencing Sphk1 inhibited the sphere formation and down-regulated the expression of stem cell-specific markers, whereas Sphk1-overexpression contributed to the maintenance of the characteristics of mammary stem cells. Sphk1 induces migration in BC cells and promotes stem cell characteristics by regulating EMT. The current findings provide a new potential for developing targeted therapy for tumor treatment.