Abstract
Wnt/β-catenin signaling is a branch of a functional network that dates back to the first metazoans and it is involved in a broad range of biological systems including stem cells, embryonic development and adult organs. Deregulation of components involved in Wnt/β-catenin signaling has been implicated in a wide spectrum of diseases including a number of cancers and degenerative diseases. The key mediator of Wnt signaling, β-catenin, serves several cellular functions. It functions in a dynamic mode at multiple cellular locations, including the plasma membrane, where β-catenin contributes to the stabilization of intercellular adhesive complexes, the cytoplasm where β-catenin levels are regulated and the nucleus where β-catenin is involved in transcriptional regulation and chromatin interactions. Central effectors of β-catenin levels are a family of cysteine-rich secreted glycoproteins, known as Wnt morphogens. Through the LRP5/6-Frizzled receptor complex, Wnts regulate the location and activity of the destruction complex and consequently intracellular β- catenin levels. However, β-catenin levels and their effects on transcriptional programs are also influenced by multiple other factors including hypoxia, inflammation, hepatocyte growth factor-mediated signaling, and the cell adhesion molecule E-cadherin. The broad implications of Wnt/β-catenin signaling in development, in the adult body and in disease render the pathway a prime target for pharmacological research and development. The intricate regulation of β-catenin at its various locations provides alternative points for therapeutic interventions.
Keywords: β-catenin, cancer, drug discovery, small molecule inhibitors, stem cells, Wnt
Current Pharmaceutical Design
Title:Wnt/beta-Catenin Signaling and Small Molecule Inhibitors
Volume: 19 Issue: 4
Author(s): Andrey Voronkov, Stefan Krauss
Affiliation:
Keywords: β-catenin, cancer, drug discovery, small molecule inhibitors, stem cells, Wnt
Abstract: Wnt/β-catenin signaling is a branch of a functional network that dates back to the first metazoans and it is involved in a broad range of biological systems including stem cells, embryonic development and adult organs. Deregulation of components involved in Wnt/β-catenin signaling has been implicated in a wide spectrum of diseases including a number of cancers and degenerative diseases. The key mediator of Wnt signaling, β-catenin, serves several cellular functions. It functions in a dynamic mode at multiple cellular locations, including the plasma membrane, where β-catenin contributes to the stabilization of intercellular adhesive complexes, the cytoplasm where β-catenin levels are regulated and the nucleus where β-catenin is involved in transcriptional regulation and chromatin interactions. Central effectors of β-catenin levels are a family of cysteine-rich secreted glycoproteins, known as Wnt morphogens. Through the LRP5/6-Frizzled receptor complex, Wnts regulate the location and activity of the destruction complex and consequently intracellular β- catenin levels. However, β-catenin levels and their effects on transcriptional programs are also influenced by multiple other factors including hypoxia, inflammation, hepatocyte growth factor-mediated signaling, and the cell adhesion molecule E-cadherin. The broad implications of Wnt/β-catenin signaling in development, in the adult body and in disease render the pathway a prime target for pharmacological research and development. The intricate regulation of β-catenin at its various locations provides alternative points for therapeutic interventions.
Export Options
About this article
Cite this article as:
Andrey Voronkov, Stefan Krauss , Wnt/beta-Catenin Signaling and Small Molecule Inhibitors, Current Pharmaceutical Design 2013; 19 (4) . https://dx.doi.org/10.2174/1381612811306040634
DOI https://dx.doi.org/10.2174/1381612811306040634 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
- Announcements
Related Articles
-
Sirtuin Inhibitors: An Overview from Medicinal Chemistry Perspective
Anti-Cancer Agents in Medicinal Chemistry The Pivotal Role of Multimodality Reporter Sensors in Drug Discovery: From Cell based Assays to Real Time Molecular Imaging
Current Pharmaceutical Biotechnology Considering Autotaxin Inhibitors in Terms of 2D-QSAR and 3D-Mapping- Review and Evaluation
Current Medicinal Chemistry The Emerging Role of EMT-related lncRNAs in Therapy Resistance and their Applications as Biomarkers
Current Medicinal Chemistry Recent Developments in Patented DC-Based Immunotherapy for Various Malignancies
Recent Patents on Regenerative Medicine Prodrugs in Genetic Chemoradiotherapy
Current Pharmaceutical Design An Epigenetic Approach to Pancreatic Cancer Treatment: The Prospective Role of Histone Deacetylase Inhibitors
Current Cancer Drug Targets Angiogenesis and Angiogenesis Inhibitors: a New Potential Anticancer Therapeutic Strategy
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Fibroblast Growth Factor Receptor Signaling in Cancer Biology and Treatment
Current Signal Transduction Therapy Matching Chelators to Radiometals for Positron Emission Tomography Imaging- Guided Targeted Drug Delivery
Current Drug Targets The Role of Blood-Brain Barrier Transporters in Pathophysiology and Pharmacotherapy of Stroke
Current Pharmaceutical Design The mTOR Pathway: A New Target in Cancer Therapy
Current Cancer Drug Targets Pharmacological Targeting of the Hsp70 Chaperone
Current Topics in Medicinal Chemistry CRISPR-Cas9, A Promising Therapeutic Tool for Cancer Therapy: A Review
Protein & Peptide Letters Expression of NRP-1 and NRP-2 in Endometrial Cancer
Current Pharmaceutical Biotechnology Impact of Drug Metabolism/Pharmacokinetics and their Relevance Upon Taxus-based Drug Development
Current Drug Metabolism Aquaporins and Roles in Brain Health and Brain Injury
Mini-Reviews in Medicinal Chemistry Cheminfomatic-based Drug Discovery of Human Tyrosine Kinase Inhibitors
Current Topics in Medicinal Chemistry A Potent Anti-Carcinoma and Anti-Acute Myeloblastic Leukemia Agent, AG490
Anti-Cancer Agents in Medicinal Chemistry Challenges in the Design of Clinically Useful Brain-targeted Drug Nanocarriers
Current Medicinal Chemistry