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.
Current Pharmaceutical Design
Title:Targeting SREBP-1-driven Lipid Metabolism to Treat Cancer
Volume: 20 Issue: 15
Author(s): Deliang Guo, Erica Hlavin Bell, Paul Mischel and Arnab Chakravarti
Affiliation:
Keywords: TCA cycle, PI3K/Akt, SREBP-1, ACLY, ACC, FASN, LDLR, LXR, ABCA1, SREBP-2.
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.
Export Options
About this article
Cite this article as:
Guo Deliang, Bell Hlavin Erica, Mischel Paul and Chakravarti Arnab, Targeting SREBP-1-driven Lipid Metabolism to Treat Cancer, Current Pharmaceutical Design 2014; 20 (15) . https://dx.doi.org/10.2174/13816128113199990486
DOI https://dx.doi.org/10.2174/13816128113199990486 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Patent Selections:
Recent Patents on Inflammation & Allergy Drug Discovery Mutations in MicroRNA Genes and Their Binding Sites are Infrequently Associated with Human Colorectal Cancer in the Kashmiri Population
MicroRNA PET Imaging of the Peripheral Benzodiazepine Receptor: Monitoring Disease Progression and Therapy Response in Neurodegenerative Disorders
Current Pharmaceutical Design A Review of Nanocarrier-Based CNS Delivery Systems
Current Drug Delivery E2F1-Mediated Apoptosis as a Target of Cancer Therapy
Current Molecular Pharmacology 1-Cyclohexylpiperazine and 3,3-Dimethylpiperidine Derivatives as Sigma-1 (σ1) and Sigma-2 (σ2) Receptor Ligands: A Review
Central Nervous System Agents in Medicinal Chemistry DNA Repair Proteins as Molecular Targets for Cancer Therapeutics
Anti-Cancer Agents in Medicinal Chemistry Signal Transducer and Activator of Transcription 3 Signaling Pathway: A Potential Target in Sarcoma Treatment
Current Enzyme Inhibition Medicinal Chemistry of Indolylglyoxylamide TSPO High Affinity Ligands with Anxiolytic-Like Effects
Current Topics in Medicinal Chemistry Phenylbutyric Acid: Simple Structure - Multiple Effects
Current Pharmaceutical Design Spermine Metabolism and Anticancer Therapy
Current Cancer Drug Targets Novel Tri-substituted Thiazoles Bearing Piperazine Ring: Synthesis and Evaluation of their Anticancer Activity
Letters in Drug Design & Discovery Rational Drug Design for Identifying Novel Multi-target Inhibitors for Hepatocellular Carcinoma
Anti-Cancer Agents in Medicinal Chemistry Anlotinib Inhibits Cell Proliferation, Migration and Invasion via Suppression of c-Met Pathway and Activation of ERK1/2 Pathway in H446 Cells
Anti-Cancer Agents in Medicinal Chemistry In Vivo Tumor Secretion Probing Via Ultrafiltration and Tissue Chamber:Implication for Anti-Cancer Drugs Targeting Secretome
Recent Patents on Anti-Cancer Drug Discovery The Alcoholic Bark Extract of <i>Terminalia Arjuna</i> Exhibits Cytotoxic and Cytostatic Activity on Jurkat Leukemia Cells
Venoms and Toxins NRG1-ErbB Lost in Translation: A New Paradigm for Lung Cancer?
Current Medicinal Chemistry Proinflammatory Cytokines in Breast Cancer: Mechanisms of Action and Potential Targets for Therapeutics
Current Drug Targets Application of Nanotechnology in the Diagnosis and Therapy of Hepatocellular Carcinoma
Recent Patents on Anti-Cancer Drug Discovery Vasotrophic Regulation of Age-Dependent Hypoxic Cerebrovascular Remodeling
Current Vascular Pharmacology