Sphingosine kinase 1 is required for migration, proliferation and survival of MCF-7 human breast cancer cells.
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.
Sarkar
Sukumar
S
Department of Biochemistry, Virginia Commonwealth University, School of Medicine, Richmond, 23298-0614, USA.
Maceyka
Michael
M
Hait
Nitai C
NC
Paugh
Steven W
SW
Sankala
Heidi
H
Milstien
Sheldon
S
Spiegel
Sarah
S
D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology*; D004789:Enzyme Activation; D006801:Humans; D009362:Neoplasm Metastasis; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000502:physiology*; D000099157:Sphingosine Kinase
D017853:Phosphotransferases (Alcohol Group Acceptor); D000099157:Sphingosine Kinase