Abstract
A family of latent cytoplasmic transcription factors, signal transducers and activators of transcription (STATs), mediates the responsiveness of cells to several cytokines and growth factors. Although mutations of STATs have not been described in human tumors, the activity of several members of the family, such as STAT1, STAT3 and STAT5, is deregulated in a variety of human tumors. STAT3 and STAT5 acquire oncogenic potential through constitutive phosphorylation on tyrosine, and their activity has been shown to be required to sustain a transformed phenotype. Disruption of STAT3 and STAT5 signaling in transformed cells therefore represents an excellent opportunity for targeted cancer therapy. In contrast to STAT3 and STAT5, STAT1 negatively regulates cell proliferation and angiogenesis and thereby inhibits tumor formation. Consistent with its tumor suppressive properties, STAT1 and its downstream targets have been shown to be reduced in a variety of human tumors and STAT1 deficient mice are highly susceptible to tumor formation. In recent years we have gained mechanistic understanding of the pathways whereby STATs convey signals from the cytoplasm to the nucleus. In addition, several endogenous regulators of the JAK/STAT pathway have been described - and their mechanism of action revealed - that profoundly affect signaling by STATs. Both should greatly facilitate the design of drugs with potential to modulate STAT signaling and to restore the homeostasis in tissues where STATs have gone awry.
Keywords: Protein Tyrosine Phosphatase (PTP), Cytokines, SOCS genes, ubiquitin-proteasome pathway, HDAC activity, TUMORS
Current Cancer Drug Targets
Title: Signal Transducers and Activators of Transcription (STATs): Novel Targets of Chemopreventive and Chemotherapeutic Drugs
Volume: 6 Issue: 2
Author(s): Lidija Klampfer
Affiliation:
Keywords: Protein Tyrosine Phosphatase (PTP), Cytokines, SOCS genes, ubiquitin-proteasome pathway, HDAC activity, TUMORS
Abstract: A family of latent cytoplasmic transcription factors, signal transducers and activators of transcription (STATs), mediates the responsiveness of cells to several cytokines and growth factors. Although mutations of STATs have not been described in human tumors, the activity of several members of the family, such as STAT1, STAT3 and STAT5, is deregulated in a variety of human tumors. STAT3 and STAT5 acquire oncogenic potential through constitutive phosphorylation on tyrosine, and their activity has been shown to be required to sustain a transformed phenotype. Disruption of STAT3 and STAT5 signaling in transformed cells therefore represents an excellent opportunity for targeted cancer therapy. In contrast to STAT3 and STAT5, STAT1 negatively regulates cell proliferation and angiogenesis and thereby inhibits tumor formation. Consistent with its tumor suppressive properties, STAT1 and its downstream targets have been shown to be reduced in a variety of human tumors and STAT1 deficient mice are highly susceptible to tumor formation. In recent years we have gained mechanistic understanding of the pathways whereby STATs convey signals from the cytoplasm to the nucleus. In addition, several endogenous regulators of the JAK/STAT pathway have been described - and their mechanism of action revealed - that profoundly affect signaling by STATs. Both should greatly facilitate the design of drugs with potential to modulate STAT signaling and to restore the homeostasis in tissues where STATs have gone awry.
Export Options
About this article
Cite this article as:
Klampfer Lidija, Signal Transducers and Activators of Transcription (STATs): Novel Targets of Chemopreventive and Chemotherapeutic Drugs, Current Cancer Drug Targets 2006; 6 (2) . https://dx.doi.org/10.2174/156800906776056491
DOI https://dx.doi.org/10.2174/156800906776056491 |
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
-
New Insight into the Mechanisms of <i>Ginkgo Biloba</i> Extract in Vascular Aging Prevention
Current Vascular Pharmacology Celecoxib Inhibits Helicobacter pylori-induced Invasion of Gastric Cancer Cells Through an Adenine Nucleotide Translocator-Dependent Mechanism
Anti-Cancer Agents in Medicinal Chemistry Biomarkers in Atrial Fibrillation; From Pathophysiology to Diagnosis and Treatment
Current Medicinal Chemistry Therapeutic Strategies of Plant-derived Compounds for Diabetes Via Regulation of Monocyte Chemoattractant Protein-1
Current Medicinal Chemistry Epigenetic Modifications: New Therapeutic Targets in Primary Myelofibrosis
Current Stem Cell Research & Therapy Subject Index to Volume 4
Current Medicinal Chemistry - Anti-Cancer Agents Effect of Conjugated Linoleic Acid Supplementation on Serum Leptin Concentration: A Systematic Review and Meta-Analysis
Endocrine, Metabolic & Immune Disorders - Drug Targets Vitamin A in Prevention of Bronchopulmonary Dysplasia
Current Pharmaceutical Design Therapeutic Potential of Drugs Targeting Pathophysiology of Intracerebral Hemorrhage: From Animal Models to Clinical Applications
Current Pharmaceutical Design Mitochondrial Injury and Targeted Intervention in Septic Cardiomyopathy
Current Pharmaceutical Design Regulatory T Cells in Atopic Dermatitis
Recent Patents on Inflammation & Allergy Drug Discovery Chemical Constituents and Biological Activities of Vietnamese Medicinal Plants
Current Topics in Medicinal Chemistry Optical Coherence Tomography Detection of Neurodegeneration in Multiple Sclerosis
CNS & Neurological Disorders - Drug Targets Exploiting Molecular Virulence Determinants in Burkholderia to Develop Vaccine Antigens
Current Medicinal Chemistry Functional Genome and Proteome Analyses of Cutaneous Autoimmune Diseases
Current Pharmaceutical Design Immune-Neuroendocrine Dysregulation in Patients with Osteoarthritis: A Revision and a Pilot Study
Endocrine, Metabolic & Immune Disorders - Drug Targets African Non Human Primates Infected by SIV - Why Dont they Get Sick? Lessons from Studies on the Early Phase of Non-Pathogenic SIV Infection
Current HIV Research Pharmacology and Perioperative Considerations of Pain Medications
Current Clinical Pharmacology The Skeletal Muscle Environment and Its Role in Immunity and Tolerance to AAV Vector-Mediated Gene Transfer
Current Gene Therapy Immunomodulatory Properties of Synthetic Imidazolone Derivatives
Letters in Drug Design & Discovery