title: Sphingosine kinase 1 is required for migration, proliferation and survival of MCF-7 human breast cancer cells.
abstract: 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.
authors.affiliation: Department of Biochemistry, Virginia Commonwealth University, School of Medicine, Richmond, 23298-0614, USA.
authors.forename: Sukumar
authors.initials: S
authors.lastname: Sarkar
authors.forename: Michael
authors.initials: M
authors.lastname: Maceyka
authors.forename: Nitai C
authors.initials: NC
authors.lastname: Hait
authors.forename: Steven W
authors.initials: SW
authors.lastname: Paugh
authors.forename: Heidi
authors.initials: H
authors.lastname: Sankala
authors.forename: Sheldon
authors.initials: S
authors.lastname: Milstien
authors.forename: Sarah
authors.initials: S
authors.lastname: Spiegel
mesh_terms: 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
chemical_list: D017853:Phosphotransferases (Alcohol Group Acceptor); D000099157:Sphingosine Kinase