| First Author | Levi L | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 8794 | PubMed ID | 26592976 |
| Mgi Jnum | J:228013 | Mgi Id | MGI:5704259 |
| Doi | 10.1038/ncomms9794 | Citation | Levi L, et al. (2015) Saturated fatty acids regulate retinoic acid signalling and suppress tumorigenesis by targeting fatty acid-binding protein 5. Nat Commun 6:8794 |
| abstractText | Long chain fatty acids (LCFA) serve as energy sources, components of cell membranes and precursors for signalling molecules. Here we show that these biological compounds also regulate gene expression and that they do so by controlling the transcriptional activities of the retinoic acid (RA)-activated nuclear receptors RAR and PPARbeta/delta. The data indicate that these activities of LCFA are mediated by FABP5, which delivers ligands from the cytosol to nuclear PPARbeta/delta. Both saturated and unsaturated LCFA (SLCFA, ULCFA) bind to FABP5, thereby displacing RA and diverting it to RAR. However, while SLCFA inhibit, ULCFA activate the FABP5/PPARbeta/delta pathway. We show further that, by concomitantly promoting the activation of RAR and inhibiting the activation of PPARbeta/delta, SLCFA suppress the oncogenic properties of FABP5-expressing carcinoma cells in cultured cells and in vivo. The observations suggest that compounds that inhibit FABP5 may constitute a new class of drugs for therapy of certain types of cancer. |
