Abstract
The CCN family of growth factors is composed of six structurally related proteins including the cysteine-rich 61 (Cyr61), connective tissue growth factor (CTGF), nephroblastoma overexpressed (NOV), Wnt-1 induced secreted protein-1 (WISP-1), WISP-2 and WISP-3. Each family member consists of four conserved cysteine rich modular domains with sequence similarity to the insulin like growth factor binding proteins, von Willebrand factor, thrombospondin repeat and the growth factors cysteine knot. The CCN proteins demonstrate a wide variety of biological activities regulating cell adhesion, proliferation, survival, migration, invasion in vitro and tumorigenesis and angiogenesis in vivo. Both cancer promoting and inhibiting roles were proposed for several CCN proteins suggesting that contextual factors could regulate their activities. Consistent with this hypothesis, structural and experimental evidence indicate that the function of these proteins is modulated by their interaction with sulfated glycosaminoglycans. Because the CCN proteins are implicated in the tumorigenic process, they are potential targets for the development of cancer therapeutics. Modulation of their glycosaminoglycan interaction by exogenous, highly sulfated polysaccharides, oligosaccharides or glycosaminoglycan mimetics could prevent their participation in cancer progression. Understanding the structural requirements for their polysaccharide interaction should provide important information to generate glycosaminoglycan-based cancer therapeutics targeting the CCN family of proteins.
Keywords: ccn proteins, proteoglycan, glycosaminoglycan, tsr, heparin binding, cancer
Current Pharmaceutical Design
Title: Structural Basis and Therapeutic Implication of the Interaction of CCN Proteins with Glycoconjugates
Volume: 10 Issue: 31
Author(s): Luc Desnoyers
Affiliation:
Keywords: ccn proteins, proteoglycan, glycosaminoglycan, tsr, heparin binding, cancer
Abstract: The CCN family of growth factors is composed of six structurally related proteins including the cysteine-rich 61 (Cyr61), connective tissue growth factor (CTGF), nephroblastoma overexpressed (NOV), Wnt-1 induced secreted protein-1 (WISP-1), WISP-2 and WISP-3. Each family member consists of four conserved cysteine rich modular domains with sequence similarity to the insulin like growth factor binding proteins, von Willebrand factor, thrombospondin repeat and the growth factors cysteine knot. The CCN proteins demonstrate a wide variety of biological activities regulating cell adhesion, proliferation, survival, migration, invasion in vitro and tumorigenesis and angiogenesis in vivo. Both cancer promoting and inhibiting roles were proposed for several CCN proteins suggesting that contextual factors could regulate their activities. Consistent with this hypothesis, structural and experimental evidence indicate that the function of these proteins is modulated by their interaction with sulfated glycosaminoglycans. Because the CCN proteins are implicated in the tumorigenic process, they are potential targets for the development of cancer therapeutics. Modulation of their glycosaminoglycan interaction by exogenous, highly sulfated polysaccharides, oligosaccharides or glycosaminoglycan mimetics could prevent their participation in cancer progression. Understanding the structural requirements for their polysaccharide interaction should provide important information to generate glycosaminoglycan-based cancer therapeutics targeting the CCN family of proteins.
Export Options
About this article
Cite this article as:
Desnoyers Luc, Structural Basis and Therapeutic Implication of the Interaction of CCN Proteins with Glycoconjugates, Current Pharmaceutical Design 2004; 10 (31) . https://dx.doi.org/10.2174/1381612043382567
DOI https://dx.doi.org/10.2174/1381612043382567 |
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
-
Complications of Muscle Hematomas in Hemophilia
Cardiovascular & Hematological Disorders-Drug Targets The Roles of Endoplasmic Reticulum Stress in the Pathophysiological Development of Cartilage and Chondrocytes
Current Pharmaceutical Design Case Report of a Large Rhinolith Cast – A Frequently Missed Diagnosis
New Emirates Medical Journal Metabolism and Structure-Function Relationships of Connective Tissue Glycosaminoglycans and Proteoglycans
Current Organic Chemistry Small-molecule Inhibitors of Epigenetic Mutations as Compelling Drugtargets for Myelodysplastic Syndromes
Current Cancer Drug Targets Notochordal Nucleus Pulposus Cells: Prospective Strategies for Intervertebral Disc Repair and Regeneration
Current Tissue Engineering (Discontinued) Flavonoids as Multi-Target Compounds in Drug Discovery
Mini-Reviews in Organic Chemistry Histone Deacetylase Inhibitors: Recent Insights from Basic to Clinical Knowledge & Patenting of Anti-Cancer Actions
Recent Patents on Anti-Cancer Drug Discovery Ewing Sarcoma Family Tumors: Past, Present and Future Prospects
Current Cancer Therapy Reviews Paeonol Inhibits Migration, Invasion and Bone Adhesion of Small Cell Lung Cancer Cells
Current Signal Transduction Therapy Dexamethasone Reduces Cell Adhesion and Migration of T47D Breast Cancer Cell Line
Anti-Cancer Agents in Medicinal Chemistry Cellular Signaling in Cartilage Tissue Engineering
Current Signal Transduction Therapy Glucosamine Sulphate in Osteoarthritis: From Symptoms to Structure Modification
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Novel Benzo[B]Furans with Anti-Microtubule Activity Upregulate Expression of Apoptotic Genes and Arrest Leukemia Cells in G2/M Phase
Anti-Cancer Agents in Medicinal Chemistry Targeting Matrix Metalloproteinases in Inflammatory Conditions
Current Drug Targets Emerging Therapies Targeting Tumor Vasculature in Multiple Myeloma and other Hematologic and Solid Malignancies
Current Cancer Drug Targets Flavonoids in Cancer Prevention
Anti-Cancer Agents in Medicinal Chemistry Chondromodulin-I and Tenomodulin: The Negative Control of Angiogenesis in Connective Tissue
Current Pharmaceutical Design Targeting CSC-Related miRNAs for Cancer Therapy by Natural Agents
Current Drug Targets NMR-based Drug Development and Improvement Against Malignant Melanoma – Implications for the MIA Protein Family
Current Medicinal Chemistry