The SDF-1alpha/CXCR4 axis induces the expression of fatty acid synthase via sterol regulatory element-binding protein-1 activation in cancer cells.
Fatty acid synthase (FASN), a key enzyme that synthesizes long-chain fatty acids, is involved in both normal lipid synthesis and cancer development. Overexpression and increased activity of FASN represents one of the most frequent phenotypic alterations in cancer cells. Multiple growth factors and growth factor receptors have emerged as major contributors to FASN overexpression. However, the ultimate mechanisms responsible for tumor-associated FASN overexpression are not completely understood. Here, we show that the stromal cell-derived factor-1 alpha (SDF-1alpha)/CXCR4 axis can induce the FASN expression via the nuclear translocation of sterol regulatory element-binding protein-1, a major modulator of FASN transcription. We also identified that recombinant SDF-1alpha-induced phosphatidylinositol-3'-kinase/protein kinase B (Akt) phosphorylation was involved in the expression or activities of FASN. Finally, we demonstrated that FASN inhibition significantly reduced the SDF-1alpha-mediated G(1) cyclin expression and cell viability. Taken together, our findings manifest that the SDF-1alpha/CXCR4 axis is a novel upstream pathway of FASN expression and is associated with mediating its prosurvival effect.
Kim
Kyeongjin
K
Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan 609-735, Republic of Korea.
Kim
Hye Young
HY
Cho
Hyun Kook
HK
Kim
Ki Hyeong
KH
Cheong
JaeHun
J
D021581:Active Transport, Cell Nucleus; D049109:Cell Proliferation; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000502:physiology*; D064429:Fatty Acid Synthases / Q000235:genetics*; D016193:G1 Phase; D006801:Humans; D009369:Neoplasms / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000502:physiology*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000502:physiology*
D054377:Chemokine CXCL12; D064429:Fatty Acid Synthases; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases; D019718:Receptors, CXCR4; D051780:Sterol Regulatory Element Binding Protein 1; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; C508053:ERBB2 protein, human