Abstract
Wnt signaling plays an important role in cancer. Signaling is initiated by binding of Wnt ligands to Frizzled cell surface receptors and results in signaling via one of three pathways, the canonical Wnt pathway, which is the best characterized in both normal tissues and in cancer, and two non-canonical Wnt pathways, the Ca2+-dependent and the PCP pathways. Canonical Wnt signaling results in β-catenin accumulation in the cytoplasm, translocation into the nucleus and activation of transcription of Wnt target genes including the c-Myc oncogene. Some cancer types, including colorectal cancer, have mutations in APC and Axin, which are involved in β-catenin phosphorylation, such that the canonical pathway is constitutively active. Few studies have investigated the role non-canonical Wnt signaling in cancer, or of Wnt signaling on tumor stromal cells. Wnt overexpression is observed in tumor stroma, as is overexpression of the Wnt pathway inhibitors, secreted Frizzled-related proteins and Dickkopf proteins. Interactions between epithelial cells and stromal cells have been observed to activate Wnt signaling in both cell types. Wnt signaling is also observed in tumor blood vessels and is likely to be activated by signals from tumor cells. Current cancer therapies focus on interfering with canonical Wnt signaling in the tumor cells. Future therapeutic targets for interfering with Wnt signaling include cell surface receptors such as the RYK and Ror2 receptors and secreted signaling molecules, which mediate signaling between cancer cells and the stromal environment.
Keywords: Wnt signaling, RYK, Ror2, stroma, cancer therapy
Current Cancer Drug Targets
Title: Importance of Wnt Signaling in the Tumor Stroma Microenvironment
Volume: 8 Issue: 6
Author(s): Maria L. Macheda and Steven A. Stacker
Affiliation:
Keywords: Wnt signaling, RYK, Ror2, stroma, cancer therapy
Abstract: Wnt signaling plays an important role in cancer. Signaling is initiated by binding of Wnt ligands to Frizzled cell surface receptors and results in signaling via one of three pathways, the canonical Wnt pathway, which is the best characterized in both normal tissues and in cancer, and two non-canonical Wnt pathways, the Ca2+-dependent and the PCP pathways. Canonical Wnt signaling results in β-catenin accumulation in the cytoplasm, translocation into the nucleus and activation of transcription of Wnt target genes including the c-Myc oncogene. Some cancer types, including colorectal cancer, have mutations in APC and Axin, which are involved in β-catenin phosphorylation, such that the canonical pathway is constitutively active. Few studies have investigated the role non-canonical Wnt signaling in cancer, or of Wnt signaling on tumor stromal cells. Wnt overexpression is observed in tumor stroma, as is overexpression of the Wnt pathway inhibitors, secreted Frizzled-related proteins and Dickkopf proteins. Interactions between epithelial cells and stromal cells have been observed to activate Wnt signaling in both cell types. Wnt signaling is also observed in tumor blood vessels and is likely to be activated by signals from tumor cells. Current cancer therapies focus on interfering with canonical Wnt signaling in the tumor cells. Future therapeutic targets for interfering with Wnt signaling include cell surface receptors such as the RYK and Ror2 receptors and secreted signaling molecules, which mediate signaling between cancer cells and the stromal environment.
Export Options
About this article
Cite this article as:
Macheda L. Maria and Stacker A. Steven, Importance of Wnt Signaling in the Tumor Stroma Microenvironment, Current Cancer Drug Targets 2008; 8 (6) . https://dx.doi.org/10.2174/156800908785699324
DOI https://dx.doi.org/10.2174/156800908785699324 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...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
Related Articles
-
Natural Compounds as Anticancer Agents Targeting DNA Topoisomerases
Current Genomics Recent Advances in Radiopharmaceutical Application of Matched-Pair Radiometals
Current Topics in Medicinal Chemistry Part I: Targeted Particles for Cancer Immunotherapy
Current Drug Delivery Molecular Markers for Individualized Therapy in Colorectal Cancer: Progress Towards a Pharmacogenomics Array
Current Pharmacogenomics and Personalized Medicine Regulation of EMT by Notch Signaling Pathway in Tumor Progression
Current Cancer Drug Targets Development of an Efficient Screening System for HDAC Inhibitor Based on TCF Response Element
Anti-Cancer Agents in Medicinal Chemistry Dermatological, Cardiovascular and Neurological Morphohistopathological Effects of Fluoropyrimidine-based Chemotherapy in Humans
Clinical Cancer Drugs Tubulins as Therapeutic Targets in Cancer: from Bench to Bedside
Current Pharmaceutical Design Molecular Dynamics in Esophageal Adenocarcinoma: Who’s in Control?
Current Cancer Drug Targets Anticancer Drugs Designed by Mother Nature: Ancient Drugs but Modern Targets
Current Pharmaceutical Design Current Status of Clinical Trials for Glioblastoma
Reviews on Recent Clinical Trials Antibody-Based Imaging of HER-2: Moving into the Clinic
Current Molecular Medicine Withdrawal Notice: Electrophoresis as a Tool for Early Cancer Diagnosis
Anti-Cancer Agents in Medicinal Chemistry Could Growth Factor-Mediated Extracellular Matrix Deposition and Degradation Offer the Ground for Directed Pharmacological Targeting in Fibrosarcoma?
Current Medicinal Chemistry Patent Selections:
Recent Patents on Anti-Cancer Drug Discovery MicroRNAs in Breast Cancer: One More Turn in Regulation
Current Drug Targets Anti-Angiogenic Peptides for Cancer Therapeutics
Current Pharmaceutical Biotechnology Personalized Medicine in Oncology: A Personal View with Myths and Facts
Current Clinical Pharmacology Chitosan Nanoparticles: A Therapeutic Carrier for Delivery of DNA, siRNA and CpG-ODNs
Nanoscience & Nanotechnology-Asia Midkine: A Promising Molecule for Drug Development to Treat Diseases of the Central Nervous System
Current Pharmaceutical Design