Abstract
Overexpression of the leucine-rich, glioma-inactivated 1 (LGI1) gene in neuroblastoma cells inhibited proliferation and efficiently induced apoptosis. Cell clones stably transfected with LGI1 cDNA showed greater mortality during a period of serum starvation in comparison with control cells stably transfected with empty vector. This observation suggested hindrance of the PI3K/Akt pathway, a central transducer of survival stimuli elicited by serum growth factors. Treatment with inhibitors of PI3K significantly increased the death of control cells but substantially failed to influence LGI1 cell death, which was greatest independently of the presence of inhibitors. Blockage of the PI3K/Akt pathway in LGI1 cells was confirmed by the lack of serum-induced Akt phosphorylation, in contrast with the strong response of control cells. Instead, serum-induced phosphorylation of ERK1/2 was not impaired by the expression of LGI1. This study showed that overexpression of LGI1 caused neuroblastoma cell death by blocking activation of the PI3K/Akt pathway. Thus, the possibility of upregulating LGI1 expression may be a novel strategy in suppressing oncogenesis and metastasis sustained by excessive activation of the PI3K/Akt pathway.
Keywords: Neuroblastoma, leucine-rich, glioma-inactivated 1 (LGI1), phosphoinositide 3-kinase (PI3K), cell death
Current Signal Transduction Therapy
Title: LGI1 Affects Survival of Neuroblastoma Cells by Inhibiting Signalling through Phosphoinositide 3-Kinase
Volume: 3 Issue: 2
Author(s): Nadia Gabellini and Valentina Masola
Affiliation:
Keywords: Neuroblastoma, leucine-rich, glioma-inactivated 1 (LGI1), phosphoinositide 3-kinase (PI3K), cell death
Abstract: Overexpression of the leucine-rich, glioma-inactivated 1 (LGI1) gene in neuroblastoma cells inhibited proliferation and efficiently induced apoptosis. Cell clones stably transfected with LGI1 cDNA showed greater mortality during a period of serum starvation in comparison with control cells stably transfected with empty vector. This observation suggested hindrance of the PI3K/Akt pathway, a central transducer of survival stimuli elicited by serum growth factors. Treatment with inhibitors of PI3K significantly increased the death of control cells but substantially failed to influence LGI1 cell death, which was greatest independently of the presence of inhibitors. Blockage of the PI3K/Akt pathway in LGI1 cells was confirmed by the lack of serum-induced Akt phosphorylation, in contrast with the strong response of control cells. Instead, serum-induced phosphorylation of ERK1/2 was not impaired by the expression of LGI1. This study showed that overexpression of LGI1 caused neuroblastoma cell death by blocking activation of the PI3K/Akt pathway. Thus, the possibility of upregulating LGI1 expression may be a novel strategy in suppressing oncogenesis and metastasis sustained by excessive activation of the PI3K/Akt pathway.
Export Options
About this article
Cite this article as:
Gabellini Nadia and Masola Valentina, LGI1 Affects Survival of Neuroblastoma Cells by Inhibiting Signalling through Phosphoinositide 3-Kinase, Current Signal Transduction Therapy 2008; 3 (2) . https://dx.doi.org/10.2174/157436208784223125
DOI https://dx.doi.org/10.2174/157436208784223125 |
Print ISSN 1574-3624 |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-389X |
- 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
-
A Novel Multiple Tyrosine-kinase Targeted Agent to Explore the Future Perspectives of Anti-Angiogenic Therapy for the Treatment of Multiple Solid Tumors: Cabozantinib
Anti-Cancer Agents in Medicinal Chemistry Caspase-Independent Pathways of Programmed Cell Death: The Unraveling of New Targets of Cancer Therapy?
Current Cancer Drug Targets Molecular Mechanisms of Pancreatic Cancer Dissemination: The Role of the Chemokine System
Current Pharmaceutical Design Honey as a Source of Dietary Antioxidants: Structures, Bioavailability and Evidence of Protective Effects Against Human Chronic Diseases
Current Medicinal Chemistry Potential of Radiolabeled PSMA PET/CT or PET/MRI Diagnostic Procedures in Gliomas/Glioblastomas
Current Radiopharmaceuticals Brain Perfusion In Sepsis
Current Vascular Pharmacology Natural Anti-inflammatory Compounds as Drug Candidates in Alzheimer’s Disease
Current Medicinal Chemistry Nanotechnology Platforms; An Innovative Approach to Brain Tumor Therapy
Medicinal Chemistry Pyruvate Dehydrogenase Kinases in the Nervous System: Their Principal Functions in Neuronal-glial Metabolic Interaction and Neuro-metabolic Disorders
Current Neuropharmacology Nanomedicine: Magnetic Nanoparticles and their Biomedical Applications
Current Medicinal Chemistry MICA Molecules in Disease and Transplantation, a Double-Edged Sword?
Current Immunology Reviews (Discontinued) Current Evaluation of the Millennium Phytomedicine- Ginseng (II): Collected Chemical Entities, Modern Pharmacology, and Clinical Applications Emanated from Traditional Chinese Medicine
Current Medicinal Chemistry A Feature-Free 30-Disease Pathological Brain Detection System by Linear Regression Classifier
CNS & Neurological Disorders - Drug Targets Protein Targeting Constructs in Alpha Therapy
Current Radiopharmaceuticals AAVs Anatomy: Roadmap for Optimizing Vectors for Translational Success
Current Gene Therapy Recent Development of CB2 Selective and Peripheral CB1/CB2 Cannabinoid Receptor Ligands
Current Medicinal Chemistry Pituitary Adenylate Cyclase Activating Polypeptide: A Potential Neuroprotective Peptide
Current Pharmaceutical Design Fabrication of Poly Hydroxybutyrate-Polyethylene Glycol-Folic Acid Nanoparticles Loaded by Paclitaxel
Current Drug Delivery Understanding the Multifaceted Role of Ectonucleotide Pyrophosphatase/Phosphodiesterase 2 (ENPP2) and its Altered Behaviour in Human Diseases
Current Molecular Medicine Highlights in Peptide Nanoparticle Carriers Intended to Oral Diseases
Current Topics in Medicinal Chemistry