| Autor: |
Williams KJ; Department of Pathology and Laboratory Medicine, University of California, Los Angeles 90095, USA., Argus JP, Zhu Y, Wilks MQ, Marbois BN, York AG, Kidani Y, Pourzia AL, Akhavan D, Lisiero DN, Komisopoulou E, Henkin AH, Soto H, Chamberlain BT, Vergnes L, Jung ME, Torres JZ, Liau LM, Christofk HR, Prins RM, Mischel PS, Reue K, Graeber TG, Bensinger SJ |
| Jazyk: |
angličtina |
| Zdroj: |
Cancer research [Cancer Res] 2013 May 01; Vol. 73 (9), pp. 2850-62. Date of Electronic Publication: 2013 Feb 25. |
| DOI: |
10.1158/0008-5472.CAN-13-0382-T |
| Abstrakt: |
The sterol regulatory element-binding proteins (SREBP) are key transcriptional regulators of lipid metabolism and cellular growth. It has been proposed that SREBP signaling regulates cellular growth through its ability to drive lipid biosynthesis. Unexpectedly, we find that loss of SREBP activity inhibits cancer cell growth and viability by uncoupling fatty acid synthesis from desaturation. Integrated lipid profiling and metabolic flux analysis revealed that cancer cells with attenuated SREBP activity maintain long-chain saturated fatty acid synthesis, while losing fatty acid desaturation capacity. We traced this defect to the uncoupling of fatty acid synthase activity from stearoyl-CoA desaturase 1 (SCD1)-mediated desaturation. This deficiency in desaturation drives an imbalance between the saturated and monounsaturated fatty acid pools resulting in severe lipotoxicity. Importantly, replenishing the monounsaturated fatty acid pool restored growth to SREBP-inhibited cells. These studies highlight the importance of fatty acid desaturation in cancer growth and provide a novel mechanistic explanation for the role of SREBPs in cancer metabolism. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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