Abstract
AKT is a central signaling molecule in regulating cell survival, proliferation, tumor growth and angiogenesis. Upstream components of AKT signaling pathway such as PI3K, PTEN, and Ras are commonly mutated in many human cancers. Recently it is found that AKT plays an important role in regulating normal vascularization and pathological angiogenesis. Angiogenesis is required for tumor growth and metastasis when tumor reaches more than 1 mm in diameter. This review focuses on the role and potential mechanism of AKT signaling in regulating angiogenesis. Recent studies have shown that AKT activation is necessary and sufficient to regulate VEGF and HIF-1 expression in human cancer cells. VEGF and HIF-1 are potent inducers of angiogenesis. It was found that AKT activation induces VEGF and HIF-1 expression through its two downstream molecules HDM2 and p70S6K1. On the other hand, AKT transmits the upstream signals from growth factors, cytokines, heavy metals, and oncogenes for regulating VEGF and HIF-1 expression in human cancer cells. AKT activation and VEGF expression can be inhibited by different natural compounds used for cancer prevention. Thus, inhibition of AKT and its downstream targets offers a new approach for targeting angiogenesis, which could be important for the development of new cancer therapeutics in the future.
Keywords: AKT, VEGF, HIF-1, tumor growth, vascularization, angiogenesis
Current Cancer Drug Targets
Title: AKT Signaling in Regulating Angiogenesis
Volume: 8 Issue: 1
Author(s): Bing-Hua Jiang and Ling-Zhi Liu
Affiliation:
Keywords: AKT, VEGF, HIF-1, tumor growth, vascularization, angiogenesis
Abstract: AKT is a central signaling molecule in regulating cell survival, proliferation, tumor growth and angiogenesis. Upstream components of AKT signaling pathway such as PI3K, PTEN, and Ras are commonly mutated in many human cancers. Recently it is found that AKT plays an important role in regulating normal vascularization and pathological angiogenesis. Angiogenesis is required for tumor growth and metastasis when tumor reaches more than 1 mm in diameter. This review focuses on the role and potential mechanism of AKT signaling in regulating angiogenesis. Recent studies have shown that AKT activation is necessary and sufficient to regulate VEGF and HIF-1 expression in human cancer cells. VEGF and HIF-1 are potent inducers of angiogenesis. It was found that AKT activation induces VEGF and HIF-1 expression through its two downstream molecules HDM2 and p70S6K1. On the other hand, AKT transmits the upstream signals from growth factors, cytokines, heavy metals, and oncogenes for regulating VEGF and HIF-1 expression in human cancer cells. AKT activation and VEGF expression can be inhibited by different natural compounds used for cancer prevention. Thus, inhibition of AKT and its downstream targets offers a new approach for targeting angiogenesis, which could be important for the development of new cancer therapeutics in the future.
Export Options
About this article
Cite this article as:
Jiang Bing-Hua and Liu Ling-Zhi, AKT Signaling in Regulating Angiogenesis, Current Cancer Drug Targets 2008; 8 (1) . https://dx.doi.org/10.2174/156800908783497122
DOI https://dx.doi.org/10.2174/156800908783497122 |
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
-
Catastrophic Antiphospholipid Syndrome - 20 Years Later
Current Rheumatology Reviews Targeting Epidermal Growth Factor Receptor in Solid Tumors: Critical Evaluation of the Biological Importance of Therapeutic Monoclonal Antibodies
Current Medicinal Chemistry Protein Arginine Deiminases and Associated Citrullination: Physiological Functions and Diseases Associated with Dysregulation
Current Drug Targets The Role of B-Lymphocyte Stimulator in Neuroendocrine Tumors: Correlation with Tumor Differentiation, Disease status and the Presence of Metastases
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Common Pathways in Health Benefit Properties of RSV in Cardiovascular Diseases, Cancers and Degenerative Pathologies
Current Pharmaceutical Biotechnology Advances in Drug Safety
Current Pharmaceutical Design Gut Microbiota as an Emerging Therapeutic Avenue for the Treatment of Nonalcoholic Fatty Liver Disease
Current Pharmaceutical Design Increased Induction of Apoptosis in ESCC (Esophageal Squamous-Cell Carcinoma) by Betula pendula Roth Stem Cell Extract Containing Triterpenoids Compared to Doxorubicin
Anti-Cancer Agents in Medicinal Chemistry Blockade of Insulin-Like Growth Factor Type-1 Receptor with Cixutumumab (IMC-A12): A Novel Approach to Treatment for Multiple Cancers
Current Drug Targets Ag+ Complexes as Potential Therapeutic Agents in Medicine and Pharmacy
Current Medicinal Chemistry Staging of Breast Cancer with 18F-FDG PET and PET/CT
Current Medical Imaging A Review on Natural Sources Derived Protein Nanoparticles as Anticancer Agents
Current Topics in Medicinal Chemistry Biomedical Applications of Carbon Nanotubes: A Critical Review
Current Drug Delivery Functions of Polo-Like Kinases: A Journey From Yeast To Humans
Protein & Peptide Letters Molecular Mechanisms of Epithelial Regeneration and Neovascularization During Healing of Gastric and Esophageal Ulcers
Current Medicinal Chemistry The Thyroid Gland: A Crossroad in Inflammation-Induced Carcinoma? An Ongoing Debate with New Therapeutic Potential.
Current Medicinal Chemistry Malignant Pleural Mesothelioma in 2011. Is there a Gold Standard Therapy?
Current Respiratory Medicine Reviews The Photodynamic Anti-Tumor Effects of New PPa-CDs Conjugate with pH Sensitivity and Improved Biocompatibility
Anti-Cancer Agents in Medicinal Chemistry Prodrugs in Genetic Chemoradiotherapy
Current Pharmaceutical Design Extranodal Marginal Zone B-Cell Lymphoma of Mucosa Associated Lymphoid Tissue Presenting as Multiple Pulmonary Lesions: Case Report and Review of the Literature
Current Respiratory Medicine Reviews