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
-
Influence of Usnic Acid and its Derivatives on the Activity of Mammalian Poly(ADP-ribose)polymerase 1 and DNA Polymerase β
Medicinal Chemistry Computer Modeling of Brain Tumor Growth
Mini-Reviews in Medicinal Chemistry The Neuroprotective Effect of Ginkgo biloba Leaf Extract and its Possible Mechanism
Central Nervous System Agents in Medicinal Chemistry Personalized Medicine for Glioblastoma: Current Challenges and Future Opportunities
Current Molecular Medicine Novel Insights into Targeting ATP-Binding Cassette Transporters for Antitumor Therapy
Current Medicinal Chemistry Anti-Cancer Effects of Citalopram on Hepatocellular Carcinoma Cells Occur via Cytochrome C Release and the Activation of NF-kB
Anti-Cancer Agents in Medicinal Chemistry Editorial [Hot Topic: SOD Enzymes and Their Mimics in Cancer:Pro- vs Anti-Oxidative Mode of Action-Part II (Guest Editor: Ines Batinic-Haberle)]
Anti-Cancer Agents in Medicinal Chemistry Interlinking of Hypoxia and Estrogen in Thyroid Cancer Progression
Current Medicinal Chemistry Apoptosis Induction by Erucylphosphohomocholine via the 18 kDa Mitochondrial Translocator Protein: Implications for Cancer Treatment
Anti-Cancer Agents in Medicinal Chemistry Targeting Cancer Stem Cell Lines as a New Treatment of Human Cancer
Recent Patents on Anti-Cancer Drug Discovery iNOS: A Potential Therapeutic Target for Malignant Glioma
Current Molecular Medicine Blockage of Autophagy in C6 Glioma Cells Enhanced Radiosensitivity Possibly by Attenuating DNA-PK-Dependent DSB Due to Limited Ku Nuclear Translocation and DNA Binding
Current Molecular Medicine Tumor Suppression by DNA Base Excision Repair
Mini-Reviews in Medicinal Chemistry Drug Resistance and Apoptosis in Cancer Treatment: Development of New Apoptosis-Inducing Agents Active in Drug Resistant Malignancies
Current Medicinal Chemistry - Anti-Cancer Agents Inhibitors of the Proteolytic Activity of Urokinase Type Plasminogen Activator
Current Pharmaceutical Design Mechanisms of Action and Chemical-Biological Interactions Between Ozone and Body Compartments: A Critical Appraisal of the Different Administration Routes
Current Drug Therapy Glyco-Nanomaterials: Translating Insights from the “Sugar-Code” to Biomedical Applications
Current Medicinal Chemistry The Synthesis and Use of Boronated Amino Acids for Boron Neutron Capture Therapy
Anti-Cancer Agents in Medicinal Chemistry Statins, Mevalonate Pathway and its Intermediate Products in Placental Development and Preeclampsia
Current Molecular Pharmacology Antibody Targeting of TGF-β in Cancer Patients
Current Pharmaceutical Biotechnology