[Frontiers in Bioscience E2, 1472-1484, June 1, 2010]

Roles of protein kinase B/Akt in lung cancer

Cheng-Xiong Xu1, Hua Jin2, Ji-Young Shin3, Ji-Eun Kim3,4, Choong-Man Hong5, Myung-Haing Cho3,4

1Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia 30322, USA, 2Center for Developmental and Therapeutics, Seattle Children`s Research Institute, Seattle, Washington 98101, USA,3Laboratory of Toxicology, College of Veterinary Medicine, 4Department of Nano Fusion Technology, Graduate School of Convergence Science and Technology Seoul National University, Seoul 151-742, Korea, 5National Institute of Food and Drug Safety, Seoul 122-704, Korea


1. Abstract
2. Introduction
3. Role of Akt signaling in lung tumorigenesis
3.1. Hyperactivation of Akt in lung cancer
3.2. Akt activated via mutation or upstream signals in lung cancer
3.3. Activated Akt stimulates lung tumorigenesis through regulation of many cellular processes
3.3.1. Activated Akt stimulates lung cancer cell growth and proliferation
3.3.2. Activated Akt attenuates apoptosis in lung cancer
3.3.3. Activated Akt increases angiogenesis in lung cancer
3.3.4. Activated Akt stimulates lung cancer metastasis
4. Role of Akt pathway in chemo- and radiotherapy resistance of lung cancer
5. Akt pathway as a therapeutic target of lung cancer
6. Summary
7. Acknowledgements
8. References


Lung cancer is the leading cause of cancer-related death worldwide and has frequently been associated with over-activated protein kinase B (PKB)/Akt. Akt is a serine/threonine protein kinase that plays an important role in cell growth, proliferation, and survival. Many lines of evidence point to the contribution of deregulated Akt in development or progression of lung cancer. In addition, recent studies have demonstrated that cancer cells defend themselves from therapeutic treatment through activation of pro-survival signals, including the Akt pathway. In this review, we described the way in which the Akt pathway is activated in development and progression of lung cancer, and the way in which deregulated Akt plays a significant role in lung tumorigenesis and resistance to chemo- or radiotherapy. In this review, we also discussed the potential of the Akt pathway as a target of lung cancer therapy.