Targeting SREBP-1-driven Lipid Metabolism to Treat Cancer

Author(s): Deliang Guo, Erica Hlavin Bell, Paul Mischel, Arnab Chakravarti

Journal Name: Current Pharmaceutical Design

Volume 20 , Issue 15 , 2014


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Abstract:

Metabolic reprogramming is a hallmark of cancer. Oncogenic growth signaling regulates glucose, glutamine and lipid metabolism to meet the bioenergetics and biosynthetic demands of rapidly proliferating tumor cells. Emerging evidence indicates that sterol regulatory element-binding protein 1 (SREBP-1), a master transcription factor that controls lipid metabolism, is a critical link between oncogenic signaling and tumor metabolism. We recently demonstrated that SREBP-1 is required for the survival of mutant EGFRcontaining glioblastoma, and that this pro-survival metabolic pathway is mediated, in part, by SREBP-1-dependent upregulation of the fatty acid synthesis and low density lipoprotein (LDL) receptor (LDLR). These results have identified EGFR/PI3K/Akt/SREBP-1 signaling pathway that promotes growth and survival in glioblastoma, and potentially other cancer types. Here, we summarize recent insights in the understanding of cancer lipid metabolism, and discuss the evidence linking SREBP-1 with PI3K/Akt signaling-controlled glycolysis and with Myc-regulated glutaminolysis to lipid metabolism. We also discuss the development of potential drugs targeting the SREBP-1- driven lipid metabolism as anti-cancer agents.

Keywords: TCA cycle, PI3K/Akt, SREBP-1, ACLY, ACC, FASN, LDLR, LXR, ABCA1, SREBP-2.

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Article Details

VOLUME: 20
ISSUE: 15
Year: 2014
Published on: 25 June, 2013
Page: [2619 - 2626]
Pages: 8
DOI: 10.2174/13816128113199990486
Price: $65

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