Abstract
Up-regulated aerobic glycolysis is a hallmark of malignant cancers. Little is understood about the reasons why malignant tumors up-regulate glycolysis and acidify their microenvironment. Signaling pathways involved in glucose changes are numerous. However, the identity of the internal glucose signal remains obscure. In this review we address the question of the significance of vacuolar proton ATPase (V-ATPase) and its relationship to up-regulated glycolysis in tumors. We know that glycolysis is extremely sensitive to changes in pH. Importantly, the V-ATPase activity is sensitive to glucose availability. Therefore, we propose that pH acts as the glucose signal via the V-ATPase that responds to changes in intracellular pH and acts as a sensor. We hypothesize that the increase in glycolysis leads to intracellular acidification and activates the V-ATPase to maintain a more alkaline intracellular pH in tumors by up-regulating glycolysis. This review attempts to provide a comprehensive description of the current knowledge about the role of V-ATPase in cancer, highlighting its role as a key player in the pH signaling pathway.
Keywords: V-ATPase, glycolysis, (Pro)Renin Receptor/ATP6ap2, Wnt/β-catenin, hypoxia-inducible factor, metastasis, glycolysis, mitochondria, microenvironment pH, plasmalemmal V-ATPase, embranes
Current Protein & Peptide Science
Title:Vacuolar H+-ATPase Signaling Pathway in Cancer
Volume: 13 Issue: 2
Author(s): Souad R. Sennoune and Raul Martinez-Zaguilan
Affiliation:
Keywords: V-ATPase, glycolysis, (Pro)Renin Receptor/ATP6ap2, Wnt/β-catenin, hypoxia-inducible factor, metastasis, glycolysis, mitochondria, microenvironment pH, plasmalemmal V-ATPase, embranes
Abstract: Up-regulated aerobic glycolysis is a hallmark of malignant cancers. Little is understood about the reasons why malignant tumors up-regulate glycolysis and acidify their microenvironment. Signaling pathways involved in glucose changes are numerous. However, the identity of the internal glucose signal remains obscure. In this review we address the question of the significance of vacuolar proton ATPase (V-ATPase) and its relationship to up-regulated glycolysis in tumors. We know that glycolysis is extremely sensitive to changes in pH. Importantly, the V-ATPase activity is sensitive to glucose availability. Therefore, we propose that pH acts as the glucose signal via the V-ATPase that responds to changes in intracellular pH and acts as a sensor. We hypothesize that the increase in glycolysis leads to intracellular acidification and activates the V-ATPase to maintain a more alkaline intracellular pH in tumors by up-regulating glycolysis. This review attempts to provide a comprehensive description of the current knowledge about the role of V-ATPase in cancer, highlighting its role as a key player in the pH signaling pathway.
Export Options
About this article
Cite this article as:
R. Sennoune Souad and Martinez-Zaguilan Raul, Vacuolar H+-ATPase Signaling Pathway in Cancer, Current Protein & Peptide Science 2012; 13 (2) . https://dx.doi.org/10.2174/138920312800493197
DOI https://dx.doi.org/10.2174/138920312800493197 |
Print ISSN 1389-2037 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5550 |
Call for Papers in Thematic Issues
Advancements in Proteomic and Peptidomic Approaches in Cancer Immunotherapy: Unveiling the Immune Microenvironment
The scope of this thematic issue centers on the integration of proteomic and peptidomic technologies into the field of cancer immunotherapy, with a particular emphasis on exploring the tumor immune microenvironment. This issue aims to gather contributions that illustrate the application of these advanced methodologies in unveiling the complex interplay ...read more
Nutrition and Metabolism in Musculoskeletal Diseases
The musculoskeletal system consists mainly of cartilage, bone, muscles, tendons, connective tissue and ligaments. Balanced metabolism is of vital importance for the homeostasis of the musculoskeletal system. A series of musculoskeletal diseases (for example, sarcopenia, osteoporosis) are resulted from the dysregulated metabolism of the musculoskeletal system. Furthermore, metabolic diseases (such ...read more
Protein Folding, Aggregation and Liquid-Liquid Phase Separation
Protein folding, misfolding and aggregation remain one of the main problems of interdisciplinary science not only because many questions are still open, but also because they are important from the point of view of practical application. Protein aggregation and formation of fibrillar structures, for example, is a hallmark of a ...read more
Related Journals
- 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
-
Novel Molecular-Targeted Therapeutics for the Treatment of Cancer
Anti-Cancer Agents in Medicinal Chemistry Clear Cell Renal Cell Cancer Tumor-Propagating Cells: Molecular Characteristics
Current Signal Transduction Therapy Recent Progress in Chemically Modified siRNAs
Mini-Reviews in Medicinal Chemistry Cell Cycle Inhibition in Malignant Lymphoma: Disease Control by Attacking the Cellular Proliferation Machinery
Current Drug Targets Cyclopamine, a Naturally Occurring Alkaloid, and Its Analogues May Find Wide Applications in Cancer Therapy
Current Topics in Medicinal Chemistry Cell-Selective Mitochondrial Targeting: Progress in Mitochondrial Medicine
Current Drug Delivery WT1 Peptide Vaccine as a Paradigm for “Cancer Antigen-Derived Peptide”-Based Immunotherapy for Malignancies: Successful Induction of Anti-Cancer Effect by Vaccination with a Single Kind of WT1 Peptide
Anti-Cancer Agents in Medicinal Chemistry Exploring Polypharmacology in Drug Discovery and Repurposing Using the CANDO Platform
Current Pharmaceutical Design Carcinogenicity and Chronic Rodent Toxicity of the Selective Progesterone Receptor Modulator Ulipristal Acetate
Current Drug Safety Targeting of Adhesion Molecules as a Therapeutic Strategy in Multiple Myeloma
Current Cancer Drug Targets Synthesis of 4-piperidone Based Curcuminoids with Anti-inflammatory and Anti-Proliferation Potential in Human Cancer Cell Lines
Anti-Cancer Agents in Medicinal Chemistry Himalayan Plants as a Source of Anti-Cancer Agents: A Review
The Natural Products Journal Pharmacokinetic Distribution of 67Cu(II)2[3,5-Diisopropyl(Carboxy- 14C)Salicylate]4 Among Murine Tissues
Current Medicinal Chemistry Small Molecules in Cancer Therapy: Cytotoxics and Molecularly Targeted Agents
Current Signal Transduction Therapy Ovarian Hyperresponse Following the Sole Administration of GnRH Agonist
Combinatorial Chemistry & High Throughput Screening Expression and Characterisation of Recombinant Molecules in Transgenic Soybean
Current Pharmaceutical Design The Type II Transmembrane Serine Protease, Matriptase-2: Possible Links to Cancer?
Anti-Cancer Agents in Medicinal Chemistry Hypertension, Anti-Hypertensive Therapy and Neoplasia
Current Pharmaceutical Design Experimental Therapy for Lung Cancer: Umbilical Cord-Derived Mesenchymal Stem Cell-Mediated Interleukin-24 Delivery
Current Cancer Drug Targets Furan-induced Oxidative Stress and DNA Damage in Diabetic and Nondiabetic Rats’ Blood and Protective Effect of Lycopene
Current Nutrition & Food Science