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
-
Inhibitors of Cancer Stem Cells
Anti-Cancer Agents in Medicinal Chemistry CXCR4-CXCL12-Dependent Inflammatory Network and Endothelial Progenitors
Current Medicinal Chemistry miRNAs Highlights in Stem and Cancer Cells
Mini-Reviews in Medicinal Chemistry Targeting Sarcomas: Novel Biological Agents and Future Perspectives
Current Drug Targets Genetics of Bladder Malignant Tumors in Childhood
Current Genomics Targeting MET Receptor in Rhabdomyosarcoma: Rationale and Progress
Current Drug Targets Classification of Sarcomas Using Bioinformatics and Molecular Profiling
Current Pharmaceutical Biotechnology Molecular Evidence of Cryptotanshinone for Treatment and Prevention of Human Cancer
Anti-Cancer Agents in 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 Blockade of Neoangiogenesis, a New and Promising Technique to Control the Growth of Malignant Tumors and their Metastases
Current Vascular Pharmacology Myostatin: Biology and Clinical Relevance
Mini-Reviews in Medicinal Chemistry Role of Forkhead Transcription Factors of the O Class (FoxO) in Development and Progression of Alzheimer’s Disease
CNS & Neurological Disorders - Drug Targets A Systematic Review of Selected Musculoskeletal Late Effects in Survivors of Childhood Cancer
Current Pediatric Reviews Nitrogen Mustards as Anticancer Chemotherapies: Historic Perspective, Current Developments and Future Trends
Current Topics in Medicinal Chemistry Network-Based Strategies Can Help Mono- and Poly-pharmacology Drug Discovery: A Systems Biology View
Current Pharmaceutical Design Systematic Analysis of RNAi Reports Identifies Dismal Commonality at Gene-Level and Reveals an Unprecedented Enrichment in Pooled shRNA Screens
Combinatorial Chemistry & High Throughput Screening Phenotypic Alteration of Bone Marrow HSC and Microenvironmental Association in Experimentally Induced Leukemia
Current Stem Cell Research & Therapy Roles of Growth Factors in Chemotherapy-Induced Intestinal Mucosal Damage Repair
Current Pharmaceutical Biotechnology Targeting Transcription Factor Binding to DNA by Competing with DNA Binders as an Approach for Controlling Gene Expression
Current Topics in Medicinal Chemistry Metal Containing Cytostatics and Their Interaction with Cellular Thiol Compounds Causing Chemoresistance
Anti-Cancer Agents in Medicinal Chemistry