|
| Status |
Public on Sep 25, 2015 |
| Title |
Saturated fatty acids regulate retinoic acid signaling and suppress tumorigenesis by targeting fatty acid-binding protein 5 |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
Long chain fatty acids (LCFA) serve as energy sources, components of cell membranes, and precursors for signalling molecules. Here we show that these important biological compounds also regulate gene expression by controlling the transcriptional activities of the retinoic acid (RA)-activated nuclear receptors RAR and PPARβ/δ. Our data indicates that these activities of LCFA are mediated by FABP5, a protein that delivers ligands from the cytosol to nuclear PPARβ/δ. Both saturated and unsaturated LCFA (SLCFA, ULCFA) tightly bind to FABP5, thereby displacing RA and diverting it to RAR. However, while SLCFA inhibit, ULCFA activate the FABP5/PPARβ/δ pathway. By concomitantly promoting the activation of RAR and inhibiting the activity of PPARβ/δ, SLCFA suppress the growth and oncogenic properties of FABP5-expressing carcinoma cells both in cultured cells and in vivo.
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| Overall design |
Mammary carcinoma line NaF was used to to examine the whole-genome effect of RAR and PPARd ligands on gene expression.
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| Contributor(s) |
Levi L, Wang Z, Doud MK, Hazen SL, Noy N |
| Citation(s) |
26592976 |
| Submission date |
Sep 18, 2015 |
| Last update date |
Mar 08, 2018 |
| Contact name |
Liraz Levi |
| E-mail(s) |
levil@ccf.org
|
| Organization name |
Lerner Research Institute; Cleveland Clinic
|
| Department |
Cellular and Molecular Medicine
|
| Lab |
Noa Noy
|
| Street address |
9500 Euclid Avenue
|
| City |
Cleveland |
| State/province |
OH |
| ZIP/Postal code |
44195 |
| Country |
USA |
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| Platforms (1) |
| GPL17400 |
[MoGene-2_1-st] Affymetrix Mouse Gene 2.1 ST Array [transcript (gene) version] |
|
| Samples (18)
|
| GSM1888236 |
cells treated with retinoic acid [RA1] |
| GSM1888237 |
cells treated with retinoic acid [RA2] |
| GSM1888238 |
cells treated with retinoic acid [RA3] |
| GSM1888239 |
cells treated with PPARd agonist, GW1516 [GW1] |
| GSM1888240 |
cells treated with PPARd agonist, GW1516 [GW2] |
| GSM1888241 |
cells treated with PPARd agonist, GW1516 [GW3] |
| GSM1888242 |
cells treated with RAR agonist, TTNPB [TTNPB1] |
| GSM1888243 |
cells treated with RAR agonist, TTNPB [TTNPB2] |
| GSM1888244 |
cells treated with RAR agonist, TTNPB [TTNPB3] |
| GSM1888245 |
untreated cells grown in full media [C1] |
| GSM1888246 |
untreated cells grown in full media [C2] |
| GSM1888247 |
untreated cells grown in full media [C3] |
| GSM1888248 |
cells grown in full media treated with palmitate [PA1] |
| GSM1888249 |
cells grown in full media treated with palmitate [PA2] |
| GSM1888250 |
cells grown in full media treated with palmitate [PA3] |
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| Relations |
| BioProject |
PRJNA296883 |
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