Sphingosine kinase 1 is required for migration, proliferation and survival of MCF-7 human breast cancer cells

FEBS Lett. 2005 Oct 10;579(24):5313-7. doi: 10.1016/j.febslet.2005.08.055.


Sphingosine-1-phosphate (S1P) is a potent lysolipid involved in a variety of biological responses important for cancer progression. Therefore, we investigated the role of sphingosine kinase type 1 (SphK1), the enzyme that makes S1P, in the motility, growth, and chemoresistance of MCF-7 breast cancer cells. Epidermal growth factor (EGF), an important growth factor for breast cancer progression, activated and translocated SphK1 to plasma membrane. SphK1 was required for EGF-directed motility. Downregulation of SphK1 in MCF-7 cells reduced EGF- and serum-stimulated growth and enhanced sensitivity to doxorubicin, a potent chemotherapeutic agent. These results suggest that SphK1 may be critical for growth, metastasis and chemoresistance of human breast cancers.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apoptosis / physiology
  • Blotting, Western
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Proliferation*
  • Cell Survival / physiology*
  • Enzyme Activation
  • Humans
  • Neoplasm Metastasis*
  • Phosphotransferases (Alcohol Group Acceptor) / physiology*


  • Phosphotransferases (Alcohol Group Acceptor)
  • sphingosine kinase