Abstract
High glucose uptake is a characteristic of most metastatic tumors and activation of Ras signaling in immortalized cells increases glycolytic flux into lactate, de novo nucleic acid synthesis and the tricarboxylic acid cycle, and increases NADH shuttling, oxygen consumption and uncoupling of ATP synthase from the proton gradient. Fructose-2,6- bisphosphate, C-Myc, HIF1α and AKT each have been found to be key regulators of glycolysis and to be controlled by Ras signaling, and there is abundant evidence for cross-talk between these regulators. The reprogramming of glycolytic and mitochondrial metabolism by Ras enables an integrated activation of energetic and anabolic pathways via the redox state of NADH that is required for the survival and growth of neoplastic cells in poorly vascularized tumors. Several small molecule antagonists specific for essential metabolic enzymes have been found to be selectively toxic to Ras-transformed cells as opposed to wild-type cells, indicating that this metabolic reprogramming and addiction may have utility for the development of anti-neoplastic agents.
Keywords: C-Myc, glycolysis, HIF1α, mitochondria, metabolism, phosphofructokinase, Ras
Current Pharmaceutical Biotechnology
Title:Regulation of Glycolytic and Mitochondrial Metabolism by Ras
Volume: 14 Issue: 3
Author(s): J. Chesney and S. Telang
Affiliation:
Keywords: C-Myc, glycolysis, HIF1α, mitochondria, metabolism, phosphofructokinase, Ras
Abstract: High glucose uptake is a characteristic of most metastatic tumors and activation of Ras signaling in immortalized cells increases glycolytic flux into lactate, de novo nucleic acid synthesis and the tricarboxylic acid cycle, and increases NADH shuttling, oxygen consumption and uncoupling of ATP synthase from the proton gradient. Fructose-2,6- bisphosphate, C-Myc, HIF1α and AKT each have been found to be key regulators of glycolysis and to be controlled by Ras signaling, and there is abundant evidence for cross-talk between these regulators. The reprogramming of glycolytic and mitochondrial metabolism by Ras enables an integrated activation of energetic and anabolic pathways via the redox state of NADH that is required for the survival and growth of neoplastic cells in poorly vascularized tumors. Several small molecule antagonists specific for essential metabolic enzymes have been found to be selectively toxic to Ras-transformed cells as opposed to wild-type cells, indicating that this metabolic reprogramming and addiction may have utility for the development of anti-neoplastic agents.
Export Options
About this article
Cite this article as:
Chesney J. and Telang S., Regulation of Glycolytic and Mitochondrial Metabolism by Ras, Current Pharmaceutical Biotechnology 2013; 14 (3) . https://dx.doi.org/10.2174/1389201011314030002
DOI https://dx.doi.org/10.2174/1389201011314030002 |
Print ISSN 1389-2010 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4316 |
Call for Papers in Thematic Issues
Artificial Intelligence in Bioinformatics
Bioinformatics is an interdisciplinary field that analyzes and explores biological data. This field combines biology and information system. Artificial Intelligence (AI) has attracted great attention as it tries to replicate human intelligence. It has become common technology for analyzing and solving complex data and problems and encompasses sub-fields of machine ...read more
- 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
Related Articles
-
Neuroimaging Features of Acquired Metabolic and Toxic Encephalopathies
Current Medical Imaging An Overview on 2-arylquinolin-4(1H)-ones and Related Structures as Tubulin Polymerisation Inhibitors
Current Topics in Medicinal Chemistry Challenges and Opportunities from Basic Cancer Biology for Nanomedicine for Targeted Drug Delivery
Current Cancer Drug Targets Adipocytes Contribute to Resistance of Human Melanoma Cells to Chemotherapy and Targeted Therapy
Current Medicinal Chemistry p53: Fighting Cancer
Current Cancer Drug Targets Vitamin D Supplementation and Cancer: Review of Randomized Controlled Trials
Anti-Cancer Agents in Medicinal Chemistry A Review on Antiproliferative and Apoptotic Activities of Natural Honey
Anti-Cancer Agents in Medicinal Chemistry Fibroblast Growth Factors, Fibroblast Growth Factor Receptors, Diseases, and Drugs
Recent Patents on Cardiovascular Drug Discovery Tailored Angiogenesis Inhibition in Cancer Therapy: Respecting the Heart to Improve the Net Outcome
Current Signal Transduction Therapy Comparative Mass Spectrometry & Nuclear Magnetic Resonance Metabolomic Approaches for Nutraceuticals Quality Control Analysis: A Brief Review
Recent Patents on Biotechnology Penetration of Tamoxifen Citrate Loaded Ethosomes and Liposomes Across Human Skin: A Comparative Study with Confocal Laser Scanning Microscopy
Current Drug Delivery <i>In Vivo</i> Evaluation of Inorganic Nanoparticle Complexes against CCL<sub>4</sub> Induced Hepatotoxicity
Current Drug Delivery Drug Development and the Importance of Ethnicity: Lessons from Heart Failure Management and Implications for Hypertension
Current Pharmaceutical Design Long Noncoding RNA MALAT1: Insights into its Biogenesis and Implications in Human Disease
Current Pharmaceutical Design Alkaloid-Metal Based Anticancer Agents
Current Topics in Medicinal Chemistry Toll-Like Receptors: Cost or Benefit for Cancer?
Current Pharmaceutical Design Cyclodextrins and their Derivatives as Carrier Molecules in Drug and Gene Delivery Systems
Current Organic Chemistry Lipoamino Acids as Major Components of Absorption Promoters in Drug Delivery
Current Topics in Medicinal Chemistry Computational Study of Imidazolylporphyrin Derivatives as a Radiopharmaceutical Ligand for Melanoma
Current Computer-Aided Drug Design Autophagy Fails to Alter Withaferin A-Mediated Lethality in Human Breast Cancer Cells
Current Cancer Drug Targets