[Frontiers in Bioscience 16, 1461-1487, January 1, 2011]

Contribution of PKB/AKT signaling to thyroid cancer

Giuseppe Viglietto1,2, Nicola Amodio1, Donatella Malanga1,2, Marianna Scrima2, Carmela De Marco1,2

1Department of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, University Campus Germaneto, Catanzaro, 88100 Italy, 2Institute for Genetic Research G. Salvatore, Ariano Irpino (AV), 83131 Italy

TABLES OF CONTENTS

1. Abstract
1. Introduction
2. Protein kinase B/Akt
3. Akt activation: upstream pathways
3.1. The phosphatidylinositol 3-kinase
3.2. The phosphatase PTEN
3.3. Ras GTPases
3.4. Tyrosine Kinase Receptors
4. Perturbations of Akt signaling in thyroid cancer
5. Signalling downstream Akt in thyroid cancer
5.1. The mTOR pathway
5.2. Apoptosis-related pathways
5.3. Proliferation-related pathways
6. Therapeutic strategies of targeting Akt signalling in thyroid cancer
7. Conclusions
8. Acknowledgments
9. References

1. ABSTRACT

The family of serine/threonine kinases B/Akt (hereafter Akt) represents a central node in signalling pathways downstream of growth factors, cytokines, and other cellular stimuli. In mammalian cells the Akt family comprises three highly homologous members -known as Akt1/PKBα, Akt2/PKBβ, and Akt3/PKBγ- that regulate several processes including cell proliferation and survival, growth and response to nutrient availability, migration, tissue invasion and angiogenesis. Aberrant activation of Akt is involved in a variety of human cancers including those arising in the thyroid gland. Here, we review the contribution of Akt-dependent pathway in the proliferation of normal thyrocytes, the different pathogenic mechanisms underlying aberrant Akt signalling in thyroid malignancies as well as the relative roles of Akt substrates that most likely contribute to the onset and/or progression of thyroid cancer. Finally, we discuss the current therapeutic strategies targeting the components of the PI3K/Akt pathway in the context of thyroid malignancy.