Abstract
Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumor in adults. Despite several advances, little is known about GBM–specific aberrant signalling processes. The hedgehog (Hh) signalling pathway plays a central role in GBM pathogenesis and tumor progression. Its activation is mediated by sonic hedgehog (Shh), which binds to its receptor patched, PTCH, promoting Gli1 activation. Gli1 is a member of the Kruppel family of zinc finger transcription factors. Hh⁄Gli1 axis controls glioma stem cells (GSCs) behaviour, which is essential to GBM chemoand radioresistance. Thus, Gli1 modulates the expression of stemness genes and the self–renewal of CD133+ GSCs. The activation of Hh⁄Gli1 in GSCs seems to be dependent on the insulin–like growth factor (IGF) signaling, which also contributes to intrinsic and acquired resistance of GSCs to temozolomide (TMZ). Beyond Hh signals, Gli1 activity is also regulated by several elements, including Ras, Myc, Akt, p53 and PTEN. Recently, a truncated variant of Gli1 (tGli1) has been demonstrated to gain the ability to regulate expression of genes that are not modulated by Gli1, such as the migration⁄invasion–associated CD24 or the human vascular endothelial growth factor–A (VEGF–A), leading to their upregulation. This review will summarize the role of Gli proteins in GBM tumorigenesis and their potential impact on GBM therapy and treatment resistance.
Keywords: Gli proteins, Glioblastoma, Glioma stem cells, Hedgehog signaling pathway, Temozolomide
Current Protein & Peptide Science
Title:Essential Role of Gli Proteins in Glioblastoma Multiforme
Volume: 14 Issue: 2
Author(s): Matteo Santoni, Luciano Burattini, Massimo Nabissi, Maria Beatrice Morelli, Rossana Berardi, Giorgio Santoni and Stefano Cascinu
Affiliation:
Keywords: Gli proteins, Glioblastoma, Glioma stem cells, Hedgehog signaling pathway, Temozolomide
Abstract: Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumor in adults. Despite several advances, little is known about GBM–specific aberrant signalling processes. The hedgehog (Hh) signalling pathway plays a central role in GBM pathogenesis and tumor progression. Its activation is mediated by sonic hedgehog (Shh), which binds to its receptor patched, PTCH, promoting Gli1 activation. Gli1 is a member of the Kruppel family of zinc finger transcription factors. Hh⁄Gli1 axis controls glioma stem cells (GSCs) behaviour, which is essential to GBM chemoand radioresistance. Thus, Gli1 modulates the expression of stemness genes and the self–renewal of CD133+ GSCs. The activation of Hh⁄Gli1 in GSCs seems to be dependent on the insulin–like growth factor (IGF) signaling, which also contributes to intrinsic and acquired resistance of GSCs to temozolomide (TMZ). Beyond Hh signals, Gli1 activity is also regulated by several elements, including Ras, Myc, Akt, p53 and PTEN. Recently, a truncated variant of Gli1 (tGli1) has been demonstrated to gain the ability to regulate expression of genes that are not modulated by Gli1, such as the migration⁄invasion–associated CD24 or the human vascular endothelial growth factor–A (VEGF–A), leading to their upregulation. This review will summarize the role of Gli proteins in GBM tumorigenesis and their potential impact on GBM therapy and treatment resistance.
Export Options
About this article
Cite this article as:
Santoni Matteo, Burattini Luciano, Nabissi Massimo, Beatrice Morelli Maria, Berardi Rossana, Santoni Giorgio and Cascinu Stefano, Essential Role of Gli Proteins in Glioblastoma Multiforme, Current Protein & Peptide Science 2013; 14 (2) . https://dx.doi.org/10.2174/1389203711314020005
DOI https://dx.doi.org/10.2174/1389203711314020005 |
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
Artificial Intelligence for Protein Research
Protein research, essential for understanding biological processes and creating therapeutics, faces challenges due to the intricate nature of protein structures and functions. Traditional methods are limited in exploring the vast protein sequence space efficiently. Artificial intelligence (AI) and machine learning (ML) offer promising solutions by improving predictions and speeding up ...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
-
The Emerging Role of Stereotactic Radiosurgery in the Treatment of Glioblastoma Multiforme
Current Radiopharmaceuticals ETS Proteins and MMPs: Partners in Invasion and Metastasis
Medicinal Chemistry Reviews - Online (Discontinued) Boronated DNA-Binding Compounds as Potential Agents for Boron Neutron Capture Therapy
Mini-Reviews in Medicinal Chemistry Part II: Targeted Particles for Imaging of Anticancer Immune Responses
Current Drug Delivery Meet Our Co-Editor
Current Signal Transduction Therapy Importance of Kier-Hall Topological Indices in the QSAR of Anticancer Drug Design
Current Computer-Aided Drug Design Antineoplastic Effects of PPARγ Agonists, with a Special Focus on Thyroid Cancer
Current Medicinal Chemistry Plasticity of Neuroendocrine-Immune Interactions During Ontogeny: Role of Perinatal Programming in Pathogenesis of Inflammation and Stress- Related Diseases in Adults
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery A Brief Evaluation of Tumor Imaging in Mice with 99mTc-glucarate Including a Comparison with 18F-FDG
Current Radiopharmaceuticals Tapasin and Human Leukocyte Antigen Class I Dysregulation Correlates with Survival in Glioblastoma Multiforme
Anti-Cancer Agents in Medicinal Chemistry Mode of Action of Long-Term Low-Dose Macrolide Therapy for Chronic Sinusitis in the Light of Neutrophil Recruitment
Current Drug Targets - Inflammation & Allergy Novel Anticancer Strategy Aimed at Targeting Shelterin Complexes by the Induction of Structural Changes in Telomeric DNA: Hitting two Birds with one Stone
Current Cancer Drug Targets Biochemical Markers of Autoimmune Diseases of the Nervous System
Current Pharmaceutical Design Prospects for Anti-Neoplastic Therapies Based on Telomere Biology
Current Cancer Drug Targets Synthesis and Evaluation of <sup>198</sup>Au/PAMAM-MPEG-FA against Cancer Cells
Anti-Cancer Agents in Medicinal Chemistry Bismuth-213 and Actinium-225 – Generator Performance and Evolving Therapeutic Applications of Two Generator-Derived Alpha-Emitting Radioisotopes
Current Radiopharmaceuticals Nanotechnology Platforms in Diagnosis and Treatment of Primary Brain Tumors
Recent Patents on Nanotechnology Statins and Protein Prenylation in Cancer Cell Biology and Therapy
Anti-Cancer Agents in Medicinal Chemistry Antiangiogenic Drugs and Tyrosine Kinases
Anti-Cancer Agents in Medicinal Chemistry A Review of the ADAMTS Family, Pharmaceutical Targets of the Future
Current Pharmaceutical Design