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
-
Processed Foods, Dysbiosis, Systemic Inflammation, and Poor Health
Current Nutrition & Food Science Targeting Gene Therapy for Prostate Cancer
Current Pharmaceutical Design High Expression of Human Leukocyte Antigen-G is Associated with a Poor Prognosis in Patients with PDAC
Current Molecular Medicine Epigenome-Wide Association Studies (EWAS) in Cancer
Current Genomics Update of the Preclinical Situation of Anticancer Platinum Complexes: Novel Design Strategies and Innovative Analytical Approaches
Current Medicinal Chemistry Preparation, Characterization, Toxicity and Pharmacodynamics of the Inclusion Complex of Brucea javanica Oil with β-cyclodextrin Polymers
Current Pharmaceutical Biotechnology Airway Stents: Current Practice and Future Directions
Current Respiratory Medicine Reviews Pleiotropic Functions of Rho GTPase Signaling: A Trojan Horse or Achilles Heel for Breast Cancer Treatment?
Current Drug Targets The Role of Stem Cells in Muscular Dystrophies
Current Gene Therapy Mechanisms of Resistance to Chemotherapy in Gastric Cancer
Anti-Cancer Agents in Medicinal Chemistry Targeting the p53-Family in Cancer and Chemosensitivity: Triple Threat
Current Drug Targets Ghrelin and Motilin in the Gastrointestinal System
Current Pharmaceutical Design Transcriptional Regulation of mPGES1 in Cancer: An Alternative Approach to Drug Discovery?
Current Drug Targets Overview of the Metallometabolomic Methodology for Metal-Based Drug Metabolism
Current Drug Metabolism Overview of the Formulations and Analogs in the Taxanes' Story
Current Medicinal Chemistry Sex Differences in Biomarkers for Predicting Cardiovascular and Coronary Events
Current Vascular Pharmacology Molecular Targets of Omega-3 Fatty Acids for Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry Collateral Damage: Contribution of Peripheral Inflammation to Neurodegenerative Diseases
Current Topics in Medicinal Chemistry Therapeutic Hypothermia as a Neuroprotective Strategy in Neonatal Hypoxic-Ischemic Brain Injury and Traumatic Brain Injury
Current Molecular Medicine Optimising the Azeotropic Drying of 18F-Fluorine Wayto Improve the 18F-Fluorocholine Radiochemical Yield
Current Radiopharmaceuticals