Grant support: The American Cancer Society (RSG-04-053-01-GMC) NIH-RO1 (CA-127892-01A), NIH-RO3 (CA-119309) and The Foreman Foundation for Melanoma Research.
The PTEN–AKT3 signaling cascade as a therapeutic target in melanoma
Article first published online: 28 MAY 2009
© 2009 John Wiley & Sons A/S. This article is a US Government work and is in the public domain in the USA
Pigment Cell & Melanoma Research
Volume 22, Issue 4, pages 400–419, August 2009
How to Cite
Madhunapantula, S. V. and Robertson, G. P. (2009), The PTEN–AKT3 signaling cascade as a therapeutic target in melanoma. Pigment Cell & Melanoma Research, 22: 400–419. doi: 10.1111/j.1755-148X.2009.00585.x
- Issue published online: 13 JUL 2009
- Article first published online: 28 MAY 2009
- PUBLICATION DATA Received 24 March 2009, revised and accepted for publication 19 May 2009
Melanocytes undergo extensive genetic changes during transformation into aggressive melanomas. These changes deregulate genes whose aberrant activity promotes the development of this disease. The phosphoinositide-3-kinase (PI3K) and mitogen-activated protein (MAP) kinase pathways are two key signaling cascades that have been found to play prominent roles in melanoma development. These pathways relay extra-cellular signals via an ordered series of consecutive phosphorylation events from cell surface throughout the cytoplasm and nucleus regulating diverse cellular processes including proliferation, survival, invasion and angiogenesis. It is generally accepted that therapeutic agents would need to target these two pathways to be an effective therapy for the long-term treatment of advanced-stage melanoma patients. This review provides an overview of the PI3 kinase pathway focusing specifically on two members of the pathway, called PTEN and Akt3, which play important roles in melanoma development. Mechanisms leading to deregulation of these two proteins and therapeutic implications of targeting this signaling cascade to treat melanoma are detailed in this review.