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- Title
The SDF-1α/CXCR4 axis induces the expression of fatty acid synthase via sterol regulatory element-binding protein-1 activation in cancer cells.
- Authors
Kim, Kyeong Jin; Kim, Hye Young; Cho, Hyun Kook; Kim, Ki Hyeong; Cheong, JaeHun
- Abstract
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-1α)/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-1α-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-1α-mediated G1 cyclin expression and cell viability. Taken together, our findings manifest that the SDF-1α/CXCR4 axis is a novel upstream pathway of FASN expression and is associated with mediating its prosurvival effect.
- Subjects
FATTY acids; STEROLS; CANCER cells; ENZYMES; PROTEINS
- Publication
Carcinogenesis, 2010, Vol 31, Issue 4, p679
- ISSN
0143-3334
- Publication type
Article
- DOI
10.1093/carcin/bgp329