Abstract
Forkhead O transcription factors (FOXO) are critical for the regulation of cell cycle arrest, cell death, and DNA damage repair. Inactivation of FOXO proteins may be associated with tumorigenesis, including breast cancer, prostate cancer, glioblastoma, rhabdomyosarcoma, and leukemia. Accumulated evidence shows that activation of oncogenic pathways such as phosphoinositide-3-kinase/AKT/IKK or RAS/mitogen-activated protein kinase suppresses FOXO transcriptional activity through the phosphorylation of FOXOs at different sites that ultimately leads to nuclear exclusion and degradation of FOXOs. In addition, posttranslational modifications of FOXOs such as acetylation, methylation and ubiquitination also contribute to modulating FOXO3a functions. Several anti-cancer drugs like paclitaxel, imatinib, and doxorubicin activate FOXO3a by counteracting those oncogenic pathways which restrain FOXOs functions. In this review, we will illustrate the regulation of FOXOs and reveal potential therapeutics that target FOXOs for cancer treatment.
Keywords: Forkhead transcriptional factor, breast cancer, cancer therapy, glioblastoma, rhabdomyosarcoma, leukemia, FoxO3, AZD6244, NSCLC
Current Drug Targets
Title: Deciphering the Role of Forkhead Transcription Factors in Cancer Therapy
Volume: 12 Issue: 9
Author(s): Jer-Yen Yang and Mien-Chie Hung
Affiliation:
Keywords: Forkhead transcriptional factor, breast cancer, cancer therapy, glioblastoma, rhabdomyosarcoma, leukemia, FoxO3, AZD6244, NSCLC
Abstract: Forkhead O transcription factors (FOXO) are critical for the regulation of cell cycle arrest, cell death, and DNA damage repair. Inactivation of FOXO proteins may be associated with tumorigenesis, including breast cancer, prostate cancer, glioblastoma, rhabdomyosarcoma, and leukemia. Accumulated evidence shows that activation of oncogenic pathways such as phosphoinositide-3-kinase/AKT/IKK or RAS/mitogen-activated protein kinase suppresses FOXO transcriptional activity through the phosphorylation of FOXOs at different sites that ultimately leads to nuclear exclusion and degradation of FOXOs. In addition, posttranslational modifications of FOXOs such as acetylation, methylation and ubiquitination also contribute to modulating FOXO3a functions. Several anti-cancer drugs like paclitaxel, imatinib, and doxorubicin activate FOXO3a by counteracting those oncogenic pathways which restrain FOXOs functions. In this review, we will illustrate the regulation of FOXOs and reveal potential therapeutics that target FOXOs for cancer treatment.
Export Options
About this article
Cite this article as:
Yang Jer-Yen and Hung Mien-Chie, Deciphering the Role of Forkhead Transcription Factors in Cancer Therapy, Current Drug Targets 2011; 12 (9) . https://dx.doi.org/10.2174/138945011796150299
DOI https://dx.doi.org/10.2174/138945011796150299 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
Call for Papers in Thematic Issues
New drug therapy for eye diseases
Eyesight is one of the most critical senses, accounting for over 80% of our perceptions. Our quality of life might be significantly affected by eye disease, including glaucoma, diabetic retinopathy, dry eye, etc. Although the development of microinvasive ocular surgery reduces surgical complications and improves overall outcomes, medication therapy is ...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
-
Aflibercept: A Novel VEGF Targeted Agent to Explore the Future Perspectives of Anti-Angiogenic Therapy for the Treatment of Multiple Tumors
Mini-Reviews in Medicinal Chemistry Nanosized Tamoxifen-Porphyrin-Glucose [TPG] Conjugate: Novel Selective Anti-breast-cancer Agent, Synthesis and In Vitro Evaluations
Medicinal Chemistry Interleukin-24: A Molecule with Potential Anti-Cancer Activity and a Cytokine in Search of a Function
Endocrine, Metabolic & Immune Disorders - Drug Targets Primary Cilia in Tumor Biology: The Primary Cilium as a Therapeutic Target in Cholangiocarcinoma
Current Drug Targets Targeting Cancer Stem Cell Lines as a New Treatment of Human Cancer
Recent Patents on Anti-Cancer Drug Discovery Roles of Nicotinic Acetylcholine Receptors in Stem Cell Survival/Apoptosis, Proliferation and Differentiation
Current Molecular Medicine From the Table to the Bedside: Can Food-Derived Sulforaphane be used as a Novel Agent to Treat Leukemia?
Current Cancer Drug Targets Recent Therapeutic Advances for Treating Medulloblastoma: Focus on New Molecular Targets
CNS & Neurological Disorders - Drug Targets Circulating Biomarkers for Tumor Angiogenesis: Where Are We?
Current Medicinal Chemistry Recent Advances in Improving Sub-Unit Vaccine Efficacy Using Cytokines as more Specific Immune Inducing Adjuvants
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Targeting Sarcomas: Novel Biological Agents and Future Perspectives
Current Drug Targets Four Major Factors Regulate Phosphatidylinositol 3-kinase Signaling Pathway in Cancers Induced by Infection of Human Papillomaviruses
Current Medicinal Chemistry Targeting Receptor Tyrosine Kinases Using Monoclonal Antibodies: The Most Specific Tools for Targeted-Based Cancer Therapy
Current Drug Targets Keratin-Based Biomaterials for Biomedical Applications
Current Drug Targets A Dilemma of Functional Genomics: Count the Chickens or Study their Eggs ?
Current Genomics Insulin-like Growth Factor: Current Concepts and New Developments in Cancer Therapy
Recent Patents on Anti-Cancer Drug Discovery Fibroblast Growth Factor Receptor Inhibitors
Current Pharmaceutical Design The Evolution of Diagnosis and Management of Pediatric Biliary Tract Rhabdomyosarcoma
Current Pediatric Reviews Targeting the PI3K/AKT/mTOR Signaling Pathway in Medulloblastoma
Current Molecular Medicine Heparanase as a Target in Cancer Therapy
Current Cancer Drug Targets